Vanishing Psammoma Bodies in the Anterior Pituitary of the Human Newborn: An Immunohistochemical and Histometric Study

Adenohypophyses of human newborns contain characteristic psammoma bodies. Their numbers are maximal within 2 weeks of the neonatal period and diminish thereafter. They are very rare in infant pituitaries, seeming to disappear by shrinkage in that there is a significant direct correlation between their number and size. The bodies were found to contain a high concentration of endogenous peroxidase, thus suggesting that the enzyme may be responsible for their disappearance. A statistical majority of psammoma bodies were located within follicular lumens. By immunohistochemistry, the follicular epithelium surrounding psammoma bodies showed immunoreactivity for various pituitary hormones. Light microscopy demonstrated that adenohypophysial cells surrounding psammoma bodies contain randomly, scattered granules or globules exhibiting peroxidase activity. Extrusion of such granules into follicular lumens may play a role in the genesis of the concretions. The conspicuous lamellar nature of the calcified psammoma bodies suggests that waves of calcium deposition occur during their morphogenesis. Despite histologic similarities, the histochemical characteristics of this type of psammoma body differ from those in other organs as well as from the calcification encountered in prolactin (PRL)-producing pituitary adenomas.     

Enhancing effects of immunization with rectal extract on rectal carcinogenesis by local X-irradiation caused in male A/HeJ mice

The influence of preimmunization with a rectal extract on X-irradiation rectal carcinogenesis in the rectum was investigated in male 4-7-week-old A/HeJ mice. They were given 20 Gy per week for a total 40 Gy in the pelvic region with or without 2 prior injections of rectal extract emulsified with complete Freund's adjuvant. Rectal adenocarcinomas were observed in 21 of 34 (62%) immunized animals and in 4 of 22 (18%) non-immunized mice 32 weeks after the last X-irradiation (P<0.01). The total incidences of adenocarcinomas at the 84 week time point were 25/45 (56%) and 12/36 (33%), respectively (P<0.05).     

Ostreopsis sp., a possible origin of palytoxin (PTX) in parrotfish Scarus ovifrons.

A clone of toxic dinoflagellate Ostreopsis sp. and six specimens of a parrotfish Scarus ovifrons were collected in October 1997 at Tokushima Prefecture, Japan. Ostreopsis sp. was cultured in ESM medium for 16 days, and after rearing the cell pellet (about 4.0x10(5) cells) was extracted with 50% methanol, partitioned between an aqueous layer and 1-butanol layer, and biochemically tested. Similarly, the crude toxin from S. ovifrons was extracted, and tested. The mice injected with each 1-butanol layer from Ostreopsis sp. and S. ovifrons showed the common symptoms of convulsion, drowsiness and collapse, and died within 48 h. The lethal potency of Ostreopsis sp. was calculated to be 1.0x10(-4) MU/cell. All specimens of S. ovifrons were found to be toxic, where the highest potency was determined as 2 MU/g in muscle of one specimen. After being injected with toxins, the serum creatine phosphokinase levels of mice were found to be elevated. Toxins from Ostreopsis sp. and S. ovifrons showed delayed haemolytic activity with mouse and human erythrocytes, which was inhibited by an anti-palytoxin (PTX) antibody antibody and ouabain. Toxins from Ostreopsis sp. and S. ovifrons thus resembled each other, and strongly suggested to be PTX or its akin substance. Additionally, a considerable number of adherent Ostreopsis sp. was found in the gut contents of S. ovifrons during the heavy occurrence of Ostreopsis sp. in October 1997 at Tokushima Prefecture. From the above results, it can be strongly postulated that the dinoflagellate Ostreopsis sp. is the origin of PTX which is sequestered by the parrotfish S. ovifrons through food chain.     

An alternative method of arterial reconstruction after hepatic arterial thrombosis following living-related liver transplantation

BACKGROUND: Hepatic artery thrombosis (HAT) remains an important cause of graft loss after liver transplantation. Emergency rearterialization methods are limited in cases of living-related liver transplantation in which the graft hepatic artery is thin and short. CASE: A 19-year-old woman who underwent living-related liver transplantation for biliary atresia developed HAT on the 4th postoperative day. During the emergency laparotomy the recipient hepatic artery was found to be too short to anastomose, so the recipient's right gastroepiploic artery was anastomosed to the graft hepatic artery. The patient is now alive and well 6 months after reoperation, and she has experienced no further episode of HAT. CONCLUSION: The right gastroepiploic artery can be used easily and safely for hepatic graft revascularization without causing ischemia of the stomach. An additional skin incision is not required, and the artery is long enough to anastomose to the graft artery directly. The method of hepatic graft rearterialization described here is an important option for patients who undergo living-related or split liver transplantation.     

Effects of transforming growth factor beta-1 and all-trans-retinoic acid on androgen-induced development of neonatal mouse bulbourethral glands in vitro

Effects of transforming growth factor beta-1 (TGF-beta1) and all-trans-retinoic acid (All-trans-RA) on development of bulbourethral glands (BUGs) of neonatal mice were investigated in vitro. BUGs from 0-day-old male mice were cultured for 6 days in serum-free, chemically defined medium containing transferrin and bovine serum albumin, supplemented with 5alpha-dihydrotestosterone (DHT; 10-8 M) and insulin (10 microg/mL) alone or in combination. Prior to culture, BUGs from 0-day-old mice consisted of a simple epithelial rudiment encapsulated by mesenchyme. Epithelial growth and ductal branching occurred in BUGs cultured in medium containing DHT and insulin or DHT alone, but epithelial branching did not occur in BUGs cultured in the presence of insulin alone. Addition of TGF-beta1 at concentrations of > 5 ng/mL (0.2 x 10-9 M) to medium containing both insulin and DHT, inhibited the expected increase in overall size of BUGs, epithelial area and ductal branching in a dose-dependent manner. TGF-beta1 also decreased [3H]-thymidine labelling indices of both epithelium and mesenchyme. TGF-beta1 at 10 ng/mL elicited these inhibitory effects on BUGs cultured in medium containing DHT alone. Addition of All-trans-RA (10-8 to 10-6 M) to the medium containing DHT plus insulin, or DHT alone did not exert significant effects on either overall size of BUGs or epithelial growth and ductal branching. All-trans-RA at 10-6 M decreased the [3H]-thymidine labelling index of mesenchyme of BUGs cultured in medium with DHT plus insulin or DHT alone, but did not decrease the [3H]-thymidine labelling index of epithelium. The present results indicate that TGF-beta1 inhibits androgen-induced epithelial and mesenchymal growth as well as epithelial morphogenesis of BUGs from neonatal mice. Such an inhibitory effect of TGF-beta1 is not mimicked by All-trans-RA at physiological concentrations.     

Activated STAT1 suppresses proliferation of cultured rat mesangial cells

BACKGROUND: JAK-STAT signaling has been shown to promote development and proliferation in lymphopoietic and hematopoietic lineages. We investigated the effect of activated STAT1 on mesangial cell proliferation. METHODS: Rat mesangial cells of primary culture (rMCs) were used in the following experiments: (1) Whole cell lysates were immunoblotted against JAK1 and JAK2. (2) Whole cell lysates and nuclear proteins were extracted from rMCs with or without treatment with interferon-gamma, and immunoblotting was performed against both STAT1 and tyrosine (701)-phosphorylated STAT1. (3) rMCs and rMCs electroporated with either wild-type STAT1, mutated STAT1, or antibody against STAT1 were incubated with interferon-gamma for 20 hours, followed by a further incubation with [3H]-thymidine for four hours. RESULTS: JAK1, JAK2, and STAT1 were detected in whole cell lysates, suggesting that JAK-STAT signaling could be activated by interferon-gamma (INF-gamma). Using an antibody specific for tyrosine-phosphorylated STAT1, we detected signal in the INF-gamma-treated nuclear extracts, which showed translocation of phosphorylated STAT1 to the nucleus. [3H]-thymidine incorporation in the presence of INF-gamma was significantly lower than that of control in a dose-dependent manner. The introduction of wild-type STAT1 enhanced the effect of interferon-gamma and decreased [3H]-thymidine incorporation, whereas tyrosine-mutated (Y701F) STAT1 and SH2 domain (R602T)-mutated STAT1 reversed INF-gamma-induced suppression of [3H]-thymidine incorporation. Electroinjected antibody against STAT1 increased [3H]-thymidine incorporation upon stimulation with INF-gamma. CONCLUSION: STAT1 activated by interferon-gamma suppresses mesangial cell proliferation.     

Gene Amplification of int-2 and erbβ in Human Esophageal Cancer: Relationship to Clinicopathological Variables

Gene amplification is a relatively frequent event in human malignant tumors and is believed to play an important role in tumor progression. The int-2 and erbB genes are amplified more frequently than any other genes in human esophageal cancer. In order to investigate the correlation between these two proto-oncogenes and the clinical behavior of esophageal cancer, we examined DNA amplification of int-2 and erbB and analyzed their relationship to clinicopathological variables. Genomic DNA was extracted from 21 esophageal squamous carcinomas and normal esopfiageal mucosa, as well as from 4 metastatic tumors. We used Southern blot analysis for detection of gene amplification. Amplification of int-2 was observed in 13 of 21 cases (62%) and in all the metastatic tumors (4/4; 100%). We found a significant correlation between amplification of int-2 and the length of the primary lesion. Amplification of erbB was detected in 3 of 18 patients (17%). All patients who showed amplification of erbB also demonstrated amplification of int-2. These results suggest that amplification of int-2 or neighboring genes on 11q may participate in tumor progression and metastasis in patients with esophageal squamous cancer.     

Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer

OBJECTIVE: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview. RESULTS: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis.     

Rapid and efficient identification of cysteine-rich peptides by random screening of a venom gland cDNA library from the hexathelid spider Macrothele gigas.

We identified novel 10 multi-cysteine peptides, namely Magi 7-16, from the spider Macrothele gigas by simple random cDNA screening of the venom gland. Mass analysis of the crude venom detected the mass numbers of the cross-linked forms of all peptides, confirming their presence in the venom. Magi 11, a C-terminus amidated peptide, was chemically synthesized and was indistinguishable from the native peptide proving the feasibility of the method for peptide identification. Moreover, toxicological assays showed diverse lethal or paralytic activities of these peptide toxins on mice and/or insects.     

Inverted variant of urothelial carcinoma of the urinary bladder: a report of three cases and a proposal for a new clinicopathologic entity

Inverted urothelial carcinoma (UC) without papillary areas is very rare; only 31 cases of three papers have been reported. The author herein reports three additional cases, and proposes the term “inverted variant” (IV) of UC. The materials were 3 cases of IV of UC, 5 cases of inverted papilloma (IP), and two cases of nested variant (NV) of UC. The three cases of IV of UC consisted of 56-year-old woman, 63-year-old man, and 78-year-old man. Presenting symptoms were hematuria in all cases. The cystoscopic findings were elevated tumors without papillary proliferations in all cases. The treatment was transurethral tumor resection (TUR-BT) in all cases. The sizes was 0.6 cm, 0.5 cm, and 3 cm. Microscopically, IV of UC showed inverted growth of atypical cells without papillary proliferations. Compared to IP, the inverted growth pattern was similar, but cytological atypia and thick trabeculae were noted in IV of UP while they were absent in IP. Compared to NV of UC, the growth pattern is different; NV of UC showed nested and vague tubular pattern. The cellular atypia is more pronounced in IV of UC than NV of UC. Immunohistochemically, p53 expression was seen in all the cases of IV of UC and in all the cases of NV of UC, while p53 expression was negative in all the cases of IP. Ki-67 labeling index was 25, 30 and 40% in IV of UC, 15 and 30% in NV of UC, and 3, 5, 6, 7, 9% in IP. Invasive features were seen in 1 case of IV of UC and 2 cases of NV of UC. In all cases of IV of UC, IP, and NV of UC, the TUR-BT, but one case of IV of UC, showed no recurrence after TUR-BT, while one case of IV of UC showed a recurrence. In conclusion, the IV and UC were structurally and cytologically very different from the NV of UC. The IV of UC was structurally similar to IP, but cellular atypia and thickened trabeculae were seen in IV and UC. p53 expression and Ki-67 labeling status were entirely different between in IV of UC and IP. The author proposes the term of IV of UC as a new clinicopathological entity.