Intermediate lymphocytic lymphoma massively involving the gastrointestinal tract

A case Is presented of intermediate lymphocytic lymphoma seen In a 53 year old mate, which extensively Infiltrated systemic organs, Including the entire digestive tract from the esophagus to the rectum. Payer's patch Invasion was evident. Multiple Intestinal perforations caused death 5 months later. Surface marker studies suggested the marginal zone origin for this CD2CT B cell malignancy.     

Aberrant insulinoma of the duodenal bulb

A rare insulin-immunoreactive neuroendocrine tumor of the duodenum in a 54 year old male is reported. The incidentally identified tumor was located on the anterior free wall of the duodenal bulb and measured approximately 6 mm in diameter. Uncomplicated endoscopic resection of the tumor was carried out. The lesion exhibited classic histologic features of insulinoma of the β-islet cell type with stromal amyloid deposition. In addition to positive reactivities of chromogranin A, neuron-specific enolase, synaptophysin, Leu 7 (CD57), cystatin C, CA15–3 and cytokeratin, the non-argyrophilic tumor cells were strongly immunoreactive for insulin and C-peptide. The stromal amyloid was clearly labeled for amylin. A few cells were stained for somato-statin, whereas other hormones were negative. Interestingly, a few isolated insulin-positive cells were identiii in the non-neoplastic duodenal mucosa in the proximity of the tumor. lmmunoelectron microscopy using paraffin sections disclosed insulin-immunoreactive secretory granules in the cytoplasm. The patient exhibited no signs or symptoms of hypoglycemia. Serum insulin levels were not measured prior to resection. No tumors were demonstrated in the pancreas. Magnetic resonance imaging revealed a 1 cm asymptomatic pituitary mass, in association with moderately elevated serum prolactin levels. The patient is currently being followed up in the outpatient clinic.     

Enhanced polymer one-step staining (EPOS) for proliferating cell nuclear antigen (PCNA) and Ki-67 antigen: Application to intra-operative frozen diagnosis

Enhanced polymer one-step staining (EPOS) is a novel, highly sensitive one-step immunostaining method. This simple and rapid technlque was applied to intra-operattve frozen diagnosis. The markers of choice were proliferating cell nuclear anmen (PCNA) and Ki-67 antigen. These cell prollferation markers were both identifiable in fresh frozen see tions of the human tonsil In approximately 7 min. The suitable staining sequences are as follows. Frozen sections prepared using 3-aminopropyitimethoxysilane-cpated glass slides are immediately fixed, without air drying, for 15s in a mixture of 50% formalin and 50% methanol for PCNA, and in 10% formalln for Ki-67 antigen. After a brief rinse in phosphate-buffered saline (PSS), sections are incubated with the EPOS antibody for 3 min, followed by PBS rinse for 1 min. The peroxidase activity is visualized in diaminobenzidine-H₂O₂ solution containing 10mmol/L imidazole for 2 min. After a light rinse in tap water, the nuclei are briefly counterstained with 5% methyl green. When necessary, endogenous peroxi-dase blockage in 1% periodic acid solution for 1 min is added before the EPOS antibody incubation. This procedure is applicable to frozen sections of gastric cancers, malignant lymphomas, and brain, liver and peritoneal lesions in which differential diagnosis between benignancy and malignancy was required.     

Specific atrial natriuretic peptide binding sites in rat cerebral capillaries

We examined the specific rat 125I-alpha-rat atrial natriuretic peptide(1-28)[ANF-(99-126)] (125I-rANP) binding sites in the cerebral capillaries from the cerebral cortex of male adult Wistar rats. The binding of 125I-rANP at 37 degrees C was saturable and of high affinity with a Kd of approximately 100 pM and Bmax of 152 fmol/mg protein. Divalent cations, Mn2+ (2.2 mM) and Ca2+ (1.8 mM) potently inhibited the binding. The rank order for inhibition of the binding was rANP, alpha-human ANP and ANF-(101-126) greater than ANF-(103-126) and ANF-(103-125)"ANF-(103-123). These data on specific binding sites of ANP in cerebral capillaries suggest a possible role for ANP in the blood-brain permeability of water and electrolytes.     

Multiple hormone production in an oat cell carcinoma of the larynx

A 60-year-old white woman with laryngeal oat cell carcinoma is described. She was a heavy smoker who had been treated seven years earlier with 5,000 rads for a well differentiated squamous cell carcinoma metastatic to a left submandibular lymph node. She presented this time with a two month history of hoarseness and tumor of the supraglottic larynx was found. There was clinical and chemical evidence of an ectopic ACTH syndrome. The histology and fine structure of the tumor were typical of oat cell carcinoma. Immunoreactive ACTH, GRP, NSE, Beta-endorphin, calcitonin, and keratin were found in the cytoplasm of the tumor cells by indirect immunoperoxidase techniques. We could find no previously reported case of laryngeal oat cell carcinoma with ectopic ACTH syndrome or cytoplasmic localization of polypeptides.     

A CASE OF GASTRIC CARCINOMA WITH MASSIVE EOSINOPHILS

This report describes a 67-year-old male with inoperable gastric cancer accompanied by marked tissue and peripheral eosinophilia without evidence of allergic disorders or parasitic infestation. Autopsy revealed an advanced gastric cancer of scirrhous type with metastases to pancreas, bone marrow, ileum, lungs, and lymph nodes. Excessive numbers of mature eosinophils were present in univolved bone marrow, liver and spleen as well as among the signet ring cell component of the cancer in either primary or metastatic sites. The primary cancer also possessed a component of tubular adenocarcinoma which was associated with only a few eosinophils. Hence, we speculate that an eosinophil mobilizing (chemotactic and/or proliferating) factor (s) was produced by the signet ring cancer cells.     

MERKEL CELL TUMOR COEXPRESSING CYTOKERATIN AND NEUROFILAMENT PROTEINS

Whorled filaments 10 nm in width were identified by anti-intermediate filaments antibodies in a Merkel cell tumor from a 52-year-old man. Immunohistochemlcal tests revealed that the tumor was stained with anti-keratin antibody and antibodies against the 68-kd and 200-kd subunits of neurofilament proteins but not antibody against the 150-kd subunlt. This is the first reported case of Merkel cell tumor expressing a 200-kd subunit of neurofilament proteins.     

High TT virus load as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease

The TT virus (TTV) load was estimated in sera obtained from 237 patients with hepatitis C virus (HCV)-related chronic liver disease including 42 patients with hepatocellular carcinoma (HCC), by real-time detection PCR using primers and a probe derived from the well-conserved untranslated region of the TTV genome, which can detect all known TTV genotypes. Of the 237 patients studied, 18 (8%) were negative for TTV DNA, 87 (37%) had low TTV viremia (1.3 x 10(2)-9.9 x 10(3) copies/ml), and 132 (56%) had high TTV viremia (1.0 x 10(4)-2.1 x 10(6) copies/ml). Various features were compared between the patients with high TTV load (n = 132) and those with no TTV viremia or low viral load (n = 105). High TTV viremia (> or =10(4) copies/ml) was significantly associated with higher age (P < 0.05), past history of blood transfusion (P < 0.001), complication of cirrhosis (P < 0.05) or HCC (P < 0.0005), lower HCV RNA titer (P < 0.05), and lower platelet count (P < 0.01). On multivariate logistic regression analysis, high TTV viral load was a significant risk factor for HCC (P < 0.05), independent from known risk factors such as complication of liver cirrhosis (P < 0.0001) and high age (> or =65 years, P < 0.05), among all 237 patients. Furthermore, high TTV viral load was an independent risk factor for HCC among the 90 cirrhotic patients (P < 0.05). These results suggest that a high TTV viral load is associated independently with the complication of HCC and may have prognostic significance in patients with HCV-related chronic liver disease, although whether high TTV viremia mediates the progression of HCV-related chronic liver disease remains to be defined.     

The effectors of killer activity induced by interferon-alpha and gamma in peripheral blood mononuclear cells

The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.     

Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure

BACKGROUND: There is broad human exposure to bisphenol A (BPA), an estrogenic endocrine-disrupting chemical widely used for the production of plastic products. BPA is reported to affect preimplantation embryos or fetuses and alter their postnatal development at doses typically found in the environment. We measured contamination of BPA in various kinds of human biological fluids by a novel enzyme-linked immunosorbent assay. METHODS: Blood samples were obtained from healthy premenopausal women, women with early and full-term pregnancy, and umbilical cord at full-term delivery. Ovarian follicular fluids obtained during IVF procedures and amniotic fluids obtained at mid-term and full-term pregnancy were also subject to BPA measurements. RESULTS: BPA was present in serum and follicular fluid at approximately 1-2 ng/ml, as well as in fetal serum and full-term amniotic fluid, confirming passage through the placenta. Surprisingly, an approximately 5-fold higher concentration, 8.3 +/- 8.7 ng/ml, was revealed in amniotic fluid at 15-18 weeks gestation, compared with other fluids. CONCLUSION: These results suggest accumulation of BPA in early fetuses and significant exposure during the prenatal period, which must be considered in evaluating the potential for human exposure to endocrine-disrupting chemicals.