Molecular Characterization of Gastrointestinal Stromal Tumors (Gist) and Contribution of Immunohistochemistry in Congolese from Kinshasa

Introduction: The differentiation of digestive tumors very often requires the use of techniques currently not widely in use in the Democratic Republic of Congo (DRC), such as immunohistochemistry. This is perfectly verified for GISTs whose precise, or at least highly certain, diagnosis can only be made using immunohistochemical markers. This underuse of these techniques due to lack of equipment and human skills explains the limited epidemiological data available to date, thus leading to untargeted and too often late treatment of patients. Research question: What contribution can immunohistochemical markers make to the diagnosis of digestive tract tumours? Objective: Discuss the contribution of immunohistochemical markers in the diagnosis of GIST and provide basic data on the epidemiology of these nosological entities in Kinshasa. Methodology: This was a retrospective study carried out at the LEBOMA private anatomy and pathological cytology centre. The main inclusion criterion was any digestive tract block or slide whose diagnosis of GIST had been requalified after review by at least 2 pathologists. An immuhistochemical study was performed using an automated technique (with a Ventana XT machine) using a panel of antibodies: CD-117 and DOG-1 which are listed in the literature as strongly correlated with the occurrence of GIST, all slides were made at Hj Hospital using an OLYMPUS BX41 co-observation microscope. Results: Of 601 cases of digestive tumors recorded during the concerned period, 32 (5.32%) concerned GIST. This prevalence was confirmed by our immunohistochemical results where the expression of CD117 and that of DOG-1 were positive in 90.6% and 100% of cases which prevalence is high compared with the worldwide prevalence according to the literature, respectively. The distribution of the patients concerned was made with a sex ratio of 1.6 women/men with a median age of 53 years. Most cases (81%) had a gastric location and were fusiform GISTs. Conclusion: Gastrointestinal stromal tumours, although rare and underestimated, account for 5.32% of cases in the DRC. This is a considerable and high prevalence compared with the world average. To the best of our knowledge, no studies have been carried out on these aspects in the DRC, which explains the importance of this study. The results of this research demonstrated the contribution of these 2 markers as specific and effective biomarkers for optimal and differential diagnosis in GIST. In view of the above, it is therefore more than necessary to popularise the use of these biomarkers in order to contribute effectively to improving the overall management of gastrointestinal tumours by improving their identification.

Influence of Socioeconomic Profile on Uptake of Immunohistochemistry Services among Women with Breast Cancer Attending Tertiary Health Facilities

Background: Breast cancer is the leading cause of death from cancer in women worldwide. It can be stratified by histological and immunopathological analysis as well as by molecular subtypes. Socioeconomic and cultural-mediated factors contribute to breast cancer heterogeneity and overall survivability. Objective: The aim of this study was to determine the influence of socioeconomic profile on the uptake of immunohistochemistry (IHC) services among women with breast cancer attending tertiary health facilities in Imo State. Methodology: This descriptive cross-sectional study was carried out among women with breast cancer in Imo State. The instrument for data collection used was a structured questionnaire constructed in line with the objectives of the study. A total of 121 respondents were selected randomly from a target study population of 891 using a systematic sampling technique. The software Statistical Package for Social Sciences (SPSS) version 21 was used for data analysis. Results: The mean age of the 121 respondents in this study was 45.2 ± 0.7 years. Age and education levels of the respondents were found to significantly influence the utilization of IHC services (P Conclusion: In our study, the consumption of IHC services was influenced significantly by the respondents’ age and level of education. Consequently, public health awareness programmes centred on the importance of IHC services in the management of breast cancer should be encouraged, so as to reach the less educationally endowed and older women in order to save more lives.

Influence of Cues to Action towards Uptake of Immunohistochemistry Services among Women with Breast Cancer Attending Tertiary Health Facilities

Background: Breast cancer is the most frequently diagnosed cancer among women, making it a significant global public health issue. Although developed countries have a higher incidence of breast cancer, developing countries like Nigeria have a low incidence rate but higher rates of morbidity and mortality from the disease. Objective: This study explored how cues to action influenced the use of immunohistochemistry by women in Imo State and how many of them used immunohistochemistry (IHC) to diagnose their condition. Methodology: We used a descriptive study methodology for the investigation, and 121 participants were chosen at random from the 891 total population. The respondents were chosen through a systematic sampling procedure. Structured questionnaire was used as the data collection tool, and the statistical software for social science (SPSS) was used to analyze the data. Results: The mean age of the 121 participants in the study was 45.2 ± 0.7 years. The study found that awareness of IHC services is a significant influencing factor for the uptake and health personnel is the major source of awareness of IHC services. Cues to action particularly from health workers, as well as knowledge of any victim of breast cancer and user of IHC services, also significantly influenced uptake of the IHC services (P Conclusion: In our study, utilization of IHC services was also impacted by cues to action, particularly from healthcare professionals, as well as awareness of any breast cancer victims and those who used IHC services thus cues to action is a major predicator of immunohistochemistry uptake among women with breast cancer.

Esophageal mesenchymal tumors:Endoscopy,pathology and immunohistochemistry

AIM： To study the endoscopic, pathological and immunoo histochemical features of esophageal mesenchymal tumors. METHODS： Twenty-nine patients diagnosed as esophageal rnysenchymal tumors by electronic endoscopy and endoscopic ultrasound （EUS） were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS： Endoscopically, esophageal gastrointestinal stromal tumors （GISTs） and leiomyomas （LMs） had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells： spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcornas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher＇s exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 （P 〉 0.05）. All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 （P 〈 0.005）. All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 115 （P 〈 0.005）. CONCLUSION： The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.

Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plasma cells was seen in AIH(90% of cases),PSC(75% of cases),and chronic hepatitis C(100% of cases),while IgMpositive plasma cells predominated in PBC(92.8% ofcases).The IgM /IgG ratio(< 1 or ≥ 1) accurately distinguished PBC from AIH in 90.9% of cases(sensitivity = 92.3%,specificity = 90%),and PBC from either AIH or PSC in 87.8% of cases(sensitivity = 92.3%,specificity = 85.7%).CONCLUSION:Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC,while other forms of liver disease analyzed in this study,including AIH,typically show an IgG-predominant plasma cell infiltrate.Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.

Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR

AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.

Molecular genetics and immunohistochemistry characterization of uncommon and recently described renal cell carcinomas

Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell （tubulo） papillary RCC, Xpl 1 translocation RCC, t（6;11） RCC, succinate dehydrogenase （SDH）-deficient RCC, acquired cystic disease- associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors （HOCT）. In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies.

Programmed cell death ligand-1(PD-L1) expression by immunohistochemistry: could it be predictive and/or prognostic in non-small cell lung cancer?

Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most studied in lung cancer,and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer(NSCLC). The reports on highprofile clinical trials have shown the association of PD-L1 expression by immunohistochemistry(IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately,however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results.The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.

Androgen receptor expression in clinically localized prostate cancer： immunohistochemistry study and literature review

Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.

Study of penetration mechanism of labrasol on rabbit cornea by Ussing chamber, RT-PCR assay, Western blot and immunohistochemistry

Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.

Neurofibrillary tangles in Alzheimer＇s disease： elucidation of the molecular mechanism by immunohistochemistry and tau protein phospho-proteomics

As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.

Comparison of Fluorescence in situ Hybridization and Immunohistochemistry for Assessment of HER-2 Status in Breast Cancer Patients

The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.

Significance of immunohistochemistry in breast cancer

The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.

Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.

THE IMMUNOHISTOCHEMISTRY AND IN SITU cDNA-mRNA HYBRIDIZATION OF CARBAMYL PHOSPHATE SYNTHETASE I IN ENZYME-ALTERED LIVER CELLS DURING CARCINOGENESIS

The changes of carbamyl phosphate synthetase I(CPS 1)in diethylnitrosamine-(DEN)-inducedenzyme-altered liver cells were studied by means of immunohistochemical(PAP)and in situcDNA-mRNA hybridization methods.The experimental rats were treated with DEN,2-acetylaminofluorene(2-AAF)and 2/3 hepatectomy according to Solt-Farber’s protocol andwere further promoted by oral daily administration of 0.05% phenobarbital in drinking water.The results showed that the average number of lesions showing abnormal expression of CPS1 was relatively constant over the course of the experiment(8 months),while the numberof normally expressing lesions gradually decreased.The former lesions were also largerin volume than the latter ones.We conclude that in DEN-initiated lesions the abnormallyexpressed CPS 1 lesions may grow continuously,thus leading to the formation of largernodules.We also suspect that some of these lesions have increased tendencies to developinto tumors.

Mycoplasma leachii causes bovine mastitis: Evidence from clinical symptoms,histopathology and immunohistochemistry

Twelve quarters of six lactating cows were inoculated with Mycoplasma leachii strain GN407 through intramammary ductal infusion; another 12 quarters were inoculated with heat-inactivated M.leachii culture medium as negative controls.Multidisciplinary procedures,including clinical assessment,etiology assessment,pathology and immunohistochemistry(IHC),were used to elucidate the pathogenicity of M.leachii in bovine mastitis.From post-inoculation days(PIDs) 3 to 9,12 inoculated quarters developed mild to severe clinical mastitis and mammary tissue histopathological changes,including inflammatory cell infiltration and architectural destruction of mammary gland ducts.The M.leachii antigen was also detected by IHC in the mammary gland epithelial cells of the inoculated quarters as a weak signal on PID 6 and as a strong signal on PID 9.The control quarters also developed mild mastitis and histopathological changes on PID 9,and M.leachii was also detected by IHC.Throughout the experimental period,the quarters of the negative control cow were clinically and pathologically normal,and the M.leachii antigen was not detected.In conclusion,direct histological and immunohistochemical evidence confirmed that M.leachii causes clinical bovine mastitis through histopathological lesions induced by invasion of the pathogen into mammary gland cells and through inflammatory cell infiltration.

Intestinal metaplasia,dysplasia and gastric cancer:a study of mucohistochemistry,immunohistochemistry and cell DNA quantitative analysis

One hundred and sixty-eight specimens of intestinal metaplasia(IM)with variousaccompanying lesions in gastric mucosa were studied with mucohistochemical and ABCimmunohistochemical staining,The quantitative analysis of cell DNA was done withflowcytometry for 36 specimens.The results indicated that the incidence of type Ⅱb IM wassignificantly higher in the groups of dysplasia(34.6％)and mucosa adjacent to gastric cancer(GC)(51.7％)than in the chronic atrophic gastritis(CAG)group(16.0％)(P【0.01).The expres-sion rate of monoclonal antibody MG7 related antigen(MG7-Ag)in type Ⅱb IM(473％)wasalso significantly higher than those in type la(29.7％),Ib(26.1％)and Ⅱa IM(28.3％)(P【0.05).Expression rate of MG7-Ag,DNA aneuploid rate and percentage of S phase cell werestatistically higher in the type Ⅱb IM with dysphsia(62.5％,62.5％ and 143±32)than in typeⅡb 1M without dysplasia(47.3％,12.5％and12.7±2.9)(P【0.05 and P【0.01).These findingssuppor the supposed progressive process:CAG→type Ⅱb IM→dysplasia→GC,andtype Ⅱb IM with dysplasia is closely associated with GC.

Microglia activation in the offspring of prenatal Poly I:C exposed rats:a PET imaging and immunohistochemistry study

Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats.Methods Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.

Histology and Immunohistochemistry Study on Mianbu Fang Healing Immunological Infertility of Male Mice

To observe the histological and immunohistochemical changes caused by of Traditional Chinese Medicine——Mianbu Fang (Immunological Infertility Healing Mixture) in testis and epididymus of male mice with immunological infertility induced by antisperm antibody (AsAb). Materials & Methods Models of mice with immunological infertility were used by injection of mice sperm. These mice were treated with Mianbu Ⅰ, Mianbu Ⅱ or Prednisone Acetates. The characteristics on histology and immunohistochemistry of mice were analyzed. Results High level of AsAb was detected in serum and seminal vesicle plasma of model mice after treatment. Immune compounds mostly deposited in limiting membrane of seminiferous tubules, spermatogonium and epithelia of epididymis ducts. The number of spermatogenic cells per convoluted seminiferous tubule decreased. However, the Chinese medicine could significantly reduce the level of AsAb, or even eliminate the antibodies and clear out the immune compounds and increase the number of spermatogenic cells of seminiferous tubules. Conclusion Chinese Medicine Mianbu Ⅰand Ⅱ can regulate, absorb and clear out circulation and partial AsAb, as well as immunological compound. Hence, they can increase the number of spermatogenic cells of seminiferous tubules and increase the pregnancy of mice.

Histopathology and Immunohistochemistry Assessments of Acute Experimental Infection by <i>Brucella melitensis</i>in Bucks

Background: Brucellosis in male goats is characterized by arthritis, orchitis and epididymitis, which may induce infertility. Nevertheless, these lesions were categorized as chronic while acute lesions had not been described. This study investigates the histopathological and immuno histochemistry reactions in organs of bucks acutely infected by Brucella melitensis. Results: Only testis and prepuce of acutely infected bucks showed significantly severe histological lesions. Other internal organs had mild to moderate lesions. However, positive immunohistochemistry stainings were observed in organs except the bulbourethral gland. There was a significant positive correlation between the distribution of B. melitensis and IHC intensity but no significant correlation between the IHC intensity and histopathology lesions. Conclusion: The results indicate that acute brucellosis did not lead to clinical presentation, although B. melitensis was well distributed in various organs of bucks.