A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2n P Library and SPOTs Method.

d-Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead-2n -peptide (OB2n P) library, which can display 2n peptide diastereomers per bead, has been developed. Through screening of the OB2n P library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-ß-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the µ-opioid receptor. The screening strategy enabled d-amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.

Asymptomatic hyponatremia due to inappropriate secretion of antidiuretic hormone as the first sign of a small cell lung cancer in an elderly man.

A 72-year-old man was hospitalized with asymptomatic hyponatremia. Despite hyponatremia, urinary sodium excretion with urine osmolality exceeding plasma osmolality persisted. Plasma vasopressin levels were high and independent of plasma osmolality during hypertonic saline infusion. Computed tomography of the chest showed enlarged mediastinal and right hilar lymph nodes. Microscopically, a specimen of lymph nodes obtained by biopsy represented vasopressin-producing small cell lung carcinoma. Chemotherapy plus irradiation improved the hyponatremia. Thus, careful evaluation is necessary to determine the cause of hyponatremia disorders in elderly patients.

Carcinosarcoma of the urinary bladder: expression of epithelial markers and different expression of heat shock proteins between epithelial and sarcomatous elements.

A case of carcinosarcoma composed of both adenocarcinoma and sarcomatous elements in the non-trigone region of the urinary bladder is presented. The epithelial element was a well to poorly differentiated adenocarcinoma with focal squamous metaplasia. The sarcomatous elements disclosed spindle cell sarcoma with focal epithelioid pattern and myxoid change in the stroma, together with chondrosarcomatous and rhabdomyosarcomatous elements. By immunohistochemical examination, not only the carcinoma element but also the sarcomatous elements showed a positive immunoreaction for cytokeratin (CK), epithelial membrane antigen (EMA) and carcinoembryonic antigen. Some population of sarcomatous elements expressed smooth muscle actin and muscle specific actin (MSA) and a limited portion of epithelioid area showed a positive immunoreaction for desmin, MSA and myoglobin, indicating leiomyosarcomatous and rhabdomyosarcomatous differentiation, respectively. Unexpectedly, tumor cells in the chondrosarcomatous element revealed a simultaneous positivity of CK and EMA as well as S-100 protein. Both epithelial and sarcomatous elements showed an intensive positive immunoreaction for p53 and heat shock protein (HSP) 70. However, HSP27 and HSP60 were detected in most epithelial elements and only in a small number of tumor cells in the sarcomatous area. These findings indicate that sarcomatous elements, including heterologous elements, may derive from epithelial elements with partial or complete loss of epithelial features, and different factors other than p53 and HSP70 may associate with the morphological alteration of carcinoma.

Splenic hemangiosarcoma with sinus endothelial differentiation.

A case of primary splenic hemangiosarcoma where the tumors entirely replaced the spleen is reported. Histologically, the splenic tumors consisted of two major components: (i) solid and nodular areas, in which spindle cells (SC) were arranged in interlacing fascicles; and (ii) vasoformative areas, in which vascular lining cells (VC) closely resembled normal splenic sinus endothelial cells (SSEC) in shape. Both SC and VC were immunoreactive with the markers of vascular endothelial cells (EC) including SSEC, JC70, von Willebrand factor, OKM5, vimentin MAb and Ulex europaeus-1 lectin. The tumor cells were positive for OKM5 MAb as well as normal SSEC and sheathed arterial EC, but other vascular EC in normal spleen were negative. Enzyme-histochemically, the tumor cells and normal SSEC revealed naphthol AS-D acetate esterase activity but no reaction for ALPase, whereas normal vascular EC other than SSEC in the spleen were positive for the latter but negative for the former. These studies revealed that the tumor cells expressed the same phenotype as normal SSEC. To the present author's knowledge this is the first report demonstrating sinus endothelial differentiation of splenic hemangiosarcoma, enzyme- and immuno-histochemically.

Hyponatremia in small cell lung cancer. Mechanisms not involving inappropriate ADH secretion.

A 62-year-old man with small cell carcinoma (oat cell type) of the lung who had hyponatremia and renal sodium loss with inappropriate antidiuresis is reported. Plasma levels of arginine vasopressin (AVP) were not elevated inappropriately. Plasma levels of atrial natriuretic peptide (ANP), however, were high, and increased after water loading and hypertonic saline infusion. The renin-aldosterone axis was normal, as were adrenal, thyroid, and renal functions. Water restriction to 500 to 700 ml/d resulted in a rise in serum sodium. Analysis of the tumor tissue failed to demonstrate the presence of AVP or ANP. The findings (1) suggest that hyponatremia and renal sodium loss with inappropriate antidiuresis observed in the patient is due to an antidiuretic substance distinct from AVP, and (2) point to the possibility that hypersecretion of ANP may play a role in the pathophysiology.