Vanadate stimulation of adenylyl cyclase: an index of tyrosine kinase vascular effects.

BACKGROUND: Beyond their mitogenic effects, hormones such as insulin, which activate receptor tyrosine kinases, regulate vascular tone. Further, we have demonstrated that receptor tyrosine kinase activation enhances adenylyl cyclase activation, a prominent mechanism that mediates vasodilation. However, whether tyrosine kinase-mediated human vascular responses parallel tyrosine kinase-mediated cellular effects on adenylyl cyclase activity is unknown. METHODS AND RESULTS: To assess tyrosine kinase-mediated vascular responses, vascular sensitivity to insulin was assessed with the dorsal hand vein linear variable differential transformer technique. Insulin infusion resulted in a dose-dependent relaxation in all subjects. Cellular responses were assessed by means of the insulinomimetic vanadate-mediated sensitization of vascular adenylyl cyclase activity. Vanadate stimulated a tyrosine kinase-dependent enhancement of adenylyl cyclase function in human and rat aortic vascular smooth muscle cells, human lymphocytes, and human aortic endothelial cells. Further, maximal insulin-mediated vasodilation was significantly positively correlated with maximal vanadate-mediated enhancement of human lymphocyte adenylyl cyclase activity. CONCLUSION: Insulin-mediated vasodilation is positively correlated with vanadate-mediated enhancement of adenylyl cyclase activity. Vanadate-mediated enhancement of adenylyl cyclase activity in lymphocytes may represent an index of tyrosine kinase-mediated vascular effects.

Proteinuria, glomerulomegaly and focal glomerulosclerosis in a grossly obese man with obstructive sleep apnea syndrome.

A grossly obese (149 kg) man with the sleep apnea syndrome was found to have proteinuria and a supernormal glomerular filtration rate. Renal histology showed glomerulomegaly and focal glomerulosclerosis. It is suggested that obesity may induce glomerular hyperfiltration and in turn glomerulosclerosis.

Sequential half-body irradiation in lymphomatoid granulomatosis. Report of a case and an immunohistologic study.

A case is presented of a man with ulcerating skin nodules who was diagnosed by histologic and immunohistologic analysis of skin biopsy specimens as having lymphomatoid granulomatosis (LYG). Phenotypic studies showed the majority of the infiltrating cells to be activated CD4+ T-lymphocytes. The disease followed a rapidly progressive course and did not respond to treatment with cytotoxic chemotherapy. The patient developed life-threatening systemic symptoms and involvement of both upper and lower respiratory tracts. After treatment with sequential half-body irradiation he has been in complete remission for 3.5 years.

A controlled trial of misonidazole in the curative treatment of infiltrating bladder cancer.

Between 1980 and 1983 a total of 89 patients with infiltrating transitional cell carcinoma of the bladder were entered in a multi centre randomised controlled clinical trial with either misonidazole or placebo added to the first 40.00 Gy of radiotherapy. Depending on their referring clinican, patients then completed treatment with either further radiotherapy to a radical dose, or surgery four weeks later. All patients have been followed up for a minimum of three years, and no significant difference has been found in local control, survival, or pathological downstaging of the tumour. The neurotoxicity was considerable, with 43% of patients receiving misonidazole developing a peripheral neuropathy, starting five weeks on average after beginning treatment, and with a mean duration of 27 months. Eighty per cent of patients affected still had peripheral neuropathy at three years or their prior death. There is a suggestion that alcohol may predispose to the neuropathy. This study failed to show any benefit of misonidazole in tumour control and produced unacceptably high levels of toxicity.

Trophoblastic metaplasia in urothelial carcinoma of the bladder.

Trophoblastic differentiation in bladder carcinoma is reported in four patients. Plasma gonadotrophin (beta subunit of HCG), measured in three patients, was elevated. In one patient treated with cisplatin, vinblastine and bleomycin, the beta HCG level fell significantly but progression of malignant disease was not arrested.

Urethral syndrome (abacterial cystitis)--search for a pathogen.

Thirty-one women with the recurrent urethral syndrome (abacterial cystitis) had extensive microbiological, cytological and histological investigations. A Streptococcus species was isolated from the bladder aspirate of one patient, a wall-deficient Streptococcus species from two others and both a Lactobacillus species and Ureaplasma urealyticum from another. A possible microbiological cause was therefore identified in the bladder in only 4 of the 31 patients. A Lactobacillus species was isolated from the bladder aspirate of one control subject. Lactobacilli were grown in the voided urine of the majority of patients and in seven of the eight control subjects. Chlamydia trachomatis and Herpes simplex were isolated from the cervix and the urethra of one patient. Urethral cytology was normal in all patients. Trigonitis was noted at cystoscopy in 26 of the 31 patients. Bladder biopsies showed squamous metaplasia in 15 and lymphocytic infiltration of the lamina propria in 29, giving support to an inflammatory aetiology of this enigmatic syndrome.

Necrobiotic xanthogranuloma: a systemic disease with paraproteinemia.

A woman of 39 presenting with a conjunctival swelling with a necrobiotic xanthogranulomatous histology suffered from a series of destructive cutaneous lesions of similar histology for 20 yr. She had a paraproteinemia and developed myelomatosis. At postmortem xanthogranulomatous lesions were found in skin, larynx, heart and kidneys. The patient also had nodular transformation of the liver with portal hypertension.

Sweat gland carcinomas in children.

The clinicopathologic features of sweat gland carcinomas in three girls and one boy, aged 7 months to 10 years, are presented. The histologic and ultrastructural features suggested malignant clear cell acrospiromas. Rapid extensive metastases developed in two and early local recurrence in one. No obvious effect of chemotherapy was noted in disseminated disease. Wide local excision is advised because of the risk of local lymphatic infiltration.

Focal glomerulosclerosis--another familial renal disease?

Of 179 consecutive patients with glomerulonephritis 27 (15 percent) had focal glomerulosclerosis (FGS). Two of these 27 patients with FGS were sisters whose mother died of renal failure at 27 years of age. The father of another of these 27 patients with FGS died from renal failure at a young age. The third family included four members who reached end-stage failure. The findings from these three families suggested that FGS may be a familial or hereditary disease.

A national trial on the treatment of invasive bladder cancer.

A new anti-cancer agent, misonidazole, is now available for investigational purposes. It is a radiation sensitiser, and a national trial is described for its use in the curative treatment of carcinoma of the bladder. The co-operation of doctors is sought in referring patients for this study.

Urate deposits in the renal medulla. Prevalence and associations.

Urate deposits within microtophi were found in 8% of unselected autopsies in Brisbane, Australia. Significant association were demonstrated with (a) a history of gouty arthritis and (b) the existence of nitrogen retention and renal disease of apparently primary, but not gouty, origin. However, in 26% of the patients, a retrospective survey of their medical records did not reveal any causative factor. The possible aetiological importance of the urine flow rate is stressed. The presence of medullary urate deposits at autopsy was most frequently associated with a history of gout or the presence of pre-existing and non-gouty renal disease, although no aetiological factor could be determined in a quarter of the cases.

A renal lesion in a woman with Reiter's disease.

A 17 year old girl with Reiter's disease had extensive involvement of the entire urinary tract in addition to arthritis, vaginitis, and ocular involvement. In addition to a severe urethritis, cystitis and ureteritis there was evidence of glomerular and tubular dysfunction and abnormalities were seen on renal biopsy. The patient was treated with a five week course of doxycycline and made a slow but complete recovery.

A renal lesion in ankylosing spondylitis.

2 patients with ankylosing spondylitis (A Sp) were found to have renal lesions similar to those seen in IgA nephropathy. In 1 patient the changes were extremely severe and progressive and in the other they were mild. Vascular changes were also noted in 1 patient. The findings suggest an immune complex mediated glomerulonephritis and support an earlier report that there may be a specific renal lesion in patients with A Sp. The significance of IgA deposition in the mesangium, and of an increase in the serum levels of IgA in some patients with A Sp is unclear.