Subcellular concentrations of estrone, estradiol, androstenedione and 17 beta-hydroxysteroid dehydrogenase (17-beta-OH-SDH) activity in malignant and non-malignant human breast tissues

Total and subcellular (cytosol and nuclear) concentrations of estrone (E1), estradiol (E2), and androstenedione were determined in non-malignant (n = 61) and malignant (n = 65) human breast tissues obtained from post-menopausal women. The 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-SDH) activity was determined in 800g supernatant fraction. Total estrogens, E1 and E2 levels and 17 beta-OH-SDH activity were significantly (p less than 0.005, 0.0005, 0.001, respectively) higher in malignant than in non-malignant breast tissues. We failed to observe significant changes in subcellular steroid concentrations or enzyme activity associated with patients' obesity or tumor estrogen receptor status. When the steroid levels were analyzed in relation to clinical staging of the disease, nuclear contents of estradiol were significantly higher (p less than 0.005) in Stage-IV patients than in those with less advanced disease (Stages I to III). 17 beta-OH-SDH activity was significantly (p less than 0.001) lower in patients with advanced disease than in those with relatively less advanced (Stages I to III) disease and was positively correlated with tissue concentration of androstenedione. Our present data indicate that differential intracellular metabolism of steroid hormones may have some influence on availability of estradiol at nuclear sites. In postmenopausal women, local interconversion of estrogens may provide sufficient estrogenic stimulus to enhance the growth and progression of breast tumors.     

Chronic administration of theophylline to rats induces a post-insulin binding defect in adipocyte glucose transport

Summary To determine whether adenosine is involved in long-term regulation of glucose transport in adipose tissue, we have investigated effects of administration of an adenosine receptor antagonist (theophylline) on adipocyte glucose transport. Rats were injected with theophylline (30 mg/kg, dissolved in 0.9% NaCl) daily for 7 days. Controls were injected with saline. The rats were then killed, and epididymal adipocytes were isolated. Insulin-stimulated glucose transport rates were decreased by about 25%–30% in the cells from theophylline-treated rats at all insulin concentrations tested. The half-maximally effective concentration of insulin was not altered (6.5±0.5 and 6.7±0.5 mU/l in control and treated cells respectively), suggesting a post-insulin binding defect. This was confirmed by the finding that ¹²⁵I-insulin binding to the cells was not altered. Adenosine receptor number and affinity (measured on detergent-solubilized adipocyte extracts using ¹²⁵I-hydroxyphenylisopropyl adenosine) was also not changed by theophylline treatment. We conclude that theophylline administration causes decreased glucose transport rates in rat adipocytes at a post-insulin binding level. Thus, chronic adenosine receptor blockade impairs adipocyte glucose transport, suggesting that adenosine is involved in long-term regulation of glucose metabolism in adipose tissue.     

Morbidity among employees engaged in the manufacture or formulation of chlorpyrifos.

The prevalence of selected illnesses and symptoms during 1977-85 was compared between 175 employees potentially exposed to the organophosphate insecticide chlorpyrifos and 335 matched controls with no history of exposure to organophosphates. Subjects were subdivided into three exposure intensity groups on the basis of job title and air monitoring data for dose response testing. This classification scheme was shown roughly to correlate with plasma cholinesterase inhibition in the workers. No statistically significant differences in illness or prevalence of symptoms were observed between the exposed and unexposed groups or among the three exposure subgroups. Potentially exposed employees did report symptoms of dizziness and of malaise and fatigue relatively more often than subjects from the comparison group; however, further analyses by exposure level, process area, or time did not support a relation with exposure. No cases of peripheral neuropathy were seen among the exposed workers. Although the sample size was small and the statistical power limited, the cumulative exposures likely to have been experienced by this workforce exceed those to be expected for individuals using the product as recommended. The absence of exposure related adverse effects, including neurological impairment, is reassuring.     

Comparative effects of pilocarpine in different vehicles on pupil diameter in albino rabbits and squirrel monkeys

Several commercial pilocarpine preparations have been compared for their efficacy of drug delivery as evaluated by changes in pupil diameter, and return to base-line pupil size, in rabbits and squirrel monkeys. Adsorbocarpine, Isoptocarpine, Pilocar, all at 2%, and Pilopine HS gel, 4%, were used. In albino rabbits the order of efficacy, as judged by area under the curve, or maximal pupil diameter change, was Pilopine greater than Isoptocarpine = Adsorbocarpine greater than Pilocar = saline (prepared in this laboratory). In general, greater areas under the curve were associated with greater changes in pupil diameter. Pupil diameter had returned to normal by a maximum of 5 hours after drop instillation. In squirrel monkeys, the maximum pupillary change was statistically (P greater than 0.05) the same for all preparations, as was the percentage change in pupil diameter at 6 hours since pupils were still somewhat constricted at this time after drop instillation. The differences in area under the curve were minor. The greater response in primates compared to rabbits may be due to differences in pigment, intraocular kinetics and a far more active ciliary muscle in primates. Also studied were newly developed, non-surfactant containing, preservative-free polymer- and microparticle-based vehicles. Some of the vehicles, based on cyanoacrylate, modified hyaluronate, anionic copolymers, polyvinyl-pyrrolidone, cross-linked gelatin and microparticles showed greater pupillary changes and areas under the curve in rabbits compared to saline vehicle. When compared to commercial preparations in the monkey eye cyanoacrylate block copolymer and modified hyaluronate showed an increase in efficacy. Polyvinylpyrrolidone, anionic copolymer and cross-linked gelatin were equal to the commercial preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Malignant histiocytosis. Complete remission in two pediatric patients

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients.     

Systemic Vasculitis with Renal Involvement — A Review

Twenty five patients with renal vasculitis presenting over an eight year period were reviewed. Ten had microscopic polyarteritis, 6 classic polyarteritis, 5 overlap syndrome, 2 Churg-Strauss syndrome and 2 Wegener’s granulomatosis. Clinical features included hypertension, pulmonary involvement, neurological involvement and arthralgia. Serum creatinine was over 500 umol/1 in 13 patients, 10 of whom required dialysis. Visceral angiography was positive in 80% of those studied, Focal and segmental necrotising glomerulonephritis was the commonest renal lesion. Treatment consisted of corticosteroids and cytotoxic agents in most cases. Plasmapheresis was used for rapidly progressive renal failure, severe pulmonary haemorrhage or cerebral vasculitis. Improvement or stabilisation of renal function was seen in 68% of patients treated. There were 4 early deaths and one late death. The diagnosis, histology, treatment and outcome of renal vasculitis is discussed. The importance of early diagnosis and treatment is emphasised in this potentially reversible cause of acute renal failure.     

Evaluation of the Ca 1 monoclonal antibody in distinguishing oral squamous cell carcinoma from non-malignant or premalignant oral lesions

The Ca antigen has been reported to be present on the surface of malignant but not, with few exceptions, non-malignant cells. We investigated the potential usefulness of the monoclonal Ca 1 antibody in differentiating oral squamous cell carcinoma from non-malignant or premalignant oral neoplasms. Paraffin-embedded sections from 33 biopsy specimens of 12 hyperplastic and 21 neoplastic oral lesions were examined by immunohistochemical staining. Seven of the 33 specimens showed positive staining for Ca antigen. Fifteen of 21 specimens of oral squamous cell carcinoma were negative for Ca antigen, and one case of focal keratosis was positive. The results indicate that the use of the Ca 1 antibody to distinguish oral squamous cell carcinoma from non-malignant or premalignant oral lesions is highly unreliable.