Clear Discrepancy in Neurofibromin Expression between NF1 Pheochromocytoma Cells and Non-Tumorous Adrenal Medullary Cells

Neurofibromatosis type 1 (NF1) is a common inherited disorder with an autosomal dominant trait. We encountered an NF1 patient who showed adrenal pheochromocytoma, and analyzed expression of neurofibromin in an excised specimen. A 54-year-old man showing multiple neurofibromas and café-au-lait spots in the skin was pointed out to have a right adrenal tumor by ultrasonography. Abdominal CT also revealed a right adrenal tumor. He was diagnosed with neurofibromatosis type 1 with no family history. Urine catecholamines, metanephrine, and normetanephrine levels were elevated. MIBG scintigraphy showed positive right adrenal uptake, and so pheochromocytoma was also diagnosed. The patient underwent laparoscopic right adrenalectomy. The excised adrenal specimen of this patient was stained with anti-neurofibromin polyclonal antibody. The NF1 pheochromocytoma was completely negative for neurofibromin protein expression, while the NF1 non-pheochromocytomatous adrenal medulla was neurofibromin-positive in the cytoplasm and nucleus. The clear discrepancy in neurofibromin expression between pheochromocytoma cells and “normal” adrenal medullary cells of the patient may well be explained by Knudson’s two-hit hypothesis.

Possible Origin of Aldosteronoma from Adrenohepatic Fusion Resulting in Intrahepatic Tumor

A 69-year-old woman was diagnosed with primary aldosteronism. An enhanced computed tomography (CT) scan before surgery indicated a right adrenal tumor outside the liver. Venous sampling tests revealed unilateral overproduction of aldosterone by the right adrenal gland. Separation of the right adrenal cortex from the liver parenchyma was impractical during a laparoscopic right adrenalectomy because of the solid attachment between the two. Therefore, the existence of adrenohepatic fusion was determined. An incision was made within the right adrenal gland, leaving completely the intrahepatic adrenal tissue on the inner side of the liver, because a partial hepatectomy was not preoperatively planned, and the patient was not informed of the consent before the surgery. Pathological examination did not reveal macro- or micro-adenomas in the resected right adrenal tissue. Aldosterone to renin ratio was as high as 1380 at 22 days following the surgery. Therefore, aldosteronoma originated from the adrenohepatic fusion that remained on the inner side of the liver was highly suspected. The patient’s blood pressure was well controlled, and she did not prefer hepatectomy to be further performed, and therefore, medical therapy was continued. When planning the type of surgery (laparoscopic or open) in these potentially confusing cases, it might be necessary to consider a possibility of the unexpected intraoperative diagnosis and the immediate measures to be performed based on the diagnosis.

Photosynthesis-Dependent Extracellular Ca2+ Influx Triggers an Asexual Reproductive Cycle in the Marine Red Macroalga Porphyra yezoensis

Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asexual life cycle are largely unknown. Here, factors involved in the regulation of production and discharge of asexual spores, so-called monospores, are identified in the marine red macroalga Porphyra yezoensis. First, enhanced discharge of monospores was found by incubation of gametophytes in ASPMT1, a modified version of the previously established synthetic medium ASP12. Comparison of the compositions of ASPMT1 and our standard medium, ESL, indicated that the Ca2+ concentration in ASPMT1 was three times lower than that in ESL medium. Thus, we modified ASPMT1 by increasing its Ca2+ concentration, resulting in reduction of monospore discharge. These findings demonstrate the role of reduced Ca2+ concentrations in enhancing monospore production and release. Moreover, it was also observed that initiation of asexual life cycle required illumination, was repressed by DCMU, and was induced by a Ca2+ ionophore in the dark. Taken together, these results indicate that photosynthesis-dependent Ca2+ influx triggers the asexual life cycle by promoting the production and discharge of monospores in P. yezoensis.

Difference in Nitrogen Starvation-Inducible Expression Patterns among Phylogenetically Diverse Ammonium Transporter Genes in the Red Seaweed <i>Pyropia yezoensis</i>

Nitrogen deficiency induces senescence and the expression of genes encoding ammonium transporters (AMTs) in terrestrial plants where the AMT family is subdivided into AMT1 and AMT2 subfamilies. Nitrogen starvation in the red seaweed Pyropia yezoensis causes senescence-like discoloration. In this study, we identified five genes in P. yezoensis encoding AMT domain-containing proteins, which were phylogenetically categorized into the AMT1 subfamily. We also found a gene encoding a Rhesus protein (Rh) that was related to, but diverged from, AMTs. Moreover, our phylogenetic analysis showed that AMT domain-containing proteins from micro- and macro-algae belonged to either the AMT1 or Rh subfamily, indicating the absence of AMT2 in algae. Gene expression analyses revealed the presence of gametophyte- and sporophyte-specific AMT1 genes that were up-regulated transiently and continually, respectively, under nitrogen-deficient conditions. In addition, up-regulated sporophyte-specific gene expression was suppressed when nitrogen was resupplied. Accordingly, an expansion of the ancient AMT gene has produced AMT1 functional variants differing in temporal and nitrogen starvation-inducible expression patterns during the life cycle of P. yezoensis. These findings help elucidate the unique nutrition starvation responses involving functionally diverse AMT1 and Rh subfamilies in red seaweed.

Phototropism in the Marine Red Macroalga Pyropia yezoensis

Phototropism is a response to the direction of light that guides growth orientation and determines the shape of plants to optimize photosynthetic activity. The phototropic response is present not only in terrestrial plants but also in water-living algae. However, knowledge about phototropism in Bangiophycean seaweeds is limited. Here, we examined the phototropic response of the red alga Pyropia yezoensis to elucidate the regulatory mechanism of phototropism in Bangiophyceae. When leafy gametophytes and filamentous sporophytes of P. yezoensis were cultured under directional light, phototropism was observed in the gametophytes. Conchosporangia on the sporophytes also exhibited phototropism. Phototropism was positive in the majority of gametophytes and conchosporangia but in some cases was negative. In addition, a strong phototropic response occurred under white light, whereas blue and red light elicited minor and no responses, respectively. This observation is in contrast with the phototropic response in terrestrial plants and several algae, in which blue light is responsible for positive phototropism. Surprisingly, the genome of P. yezoensis has no homologues of the photoreceptors for blue and red light, revealing differences in the regulation of phototropism between terrestrial plants and P. yezoensis . Studies on the phototropism in P. yezoensis could shed light on the evolutional divergence of phototropic responses in plants.

HMGB1 and HMGB2 Expression Patterns in Human Papillary Renal Cancers

High mobility group box (HMGB) proteins are nuclear nonhistone chromosomal proteins that bend DNA, bind preferentially to distorted DNA structures, and promote the assembly of site-specific DNA binding proteins. Recent reports indicate that HMGB1 has a dual function, a cytokine in addition to a nuclear protein. The increased expression of HMGB1 has been reported for several different tumors. Here, we assessed HMGB1 and HMGB2 expressions in two cases of papillary renal cell carcinoma. One case with pT1a, Grade 2 showed HMGB1 expression in the nucleus and cytosol and HMGB2 expression in the nucleus, but not in the cytosol. In the other case, there were three renal tumors, one of which was clear cell renal cell carcinoma with pT1a, Grade 3 and two were papillary renal cell carcinomas, Grade 2 (5 mmand2 mmin the diameter). Both HMGB1 and HMGB2 were expressed in the nucleus and cytosol of papillary carcinoma. In the clear cell carcinoma of this case, HMGB1 expression was stained both in the nucleus and cytosol, while HMGB2 was observed in the nucleus, but not in the cytosol. More samples need to be further investigated in order to draw conclusions concerning HMGB expressions in papillary renal cell carcinomas.

A Case of Incidentally Found Bilateral Retroperitoneal Cavernous Hemangiomas

A 59-year-old male was admitted to our hospital because of incidentally found right retroperitoneal tumor. He had undergone removal of a hemangioma in the left oral cavity four years before. An abdominal CT scan performed in our hospital revealed poorly enhanced bilateral retroperitoneal tumors adjacent to kidneys. Those tumors were of low signal intensity on T1-weighted images and high on T2-weighted images by magnetic resonance imaging. The right retroperitoneal tumor of 2.5 cm in size was surgically removed and histopathological examination indicated cavernous hemangioma. The smaller left retroperitoneal tumor of 1.1 cm in size was left untouched to be followed up, as we supposed that it has the same benign pathology. There have been no previous cases of retroperitoneal cavernous hemangioma as a presentation of multiple hemangiomas.

A radiation-related second primary gastrointestinal stromal tumor in the bladder

A 69-year-old man underwent 78 Gy/39 Fr of intensity-modulated radiation therapy for prostate cancer.Seven years after radiotherapy,a nonpapillary bladder tumor was identified.Transurethral resection of the bladder tumor was performed,and the pathological diagnosis was spindle cell sarcoma.Immunostaining revealed KIT^(-),DOG1^(++),CD34^(-),Actin^(++),Cytokeratin^(-),Desmin^(-),S100 protein^(-),and Vmentin^(++).No tumor recurrence was observed until 17 months after tumor resection.DOG1 is strongly and specifically expressed in gastrointestinal stromal tumors.This was a rare case of bladder gastrointestinal stromal tumor as a radiation-related second primary tumor.