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Biomedical subjects

J B Miller

Publications and source records attributed to J B Miller.

At least 145 records · Page 8Linked to original sources
PubMed1984

Progesterone production by ectopic corpora lutea is independent of luteinizing hormone-stimulated adenylyl cyclase during early luteal development in the rabbit.

Although estradiol is luteotropic in rabbits, corpora lutea develop and secrete progesterone in the absence of estradiol for 4-5 days. This period of estradiol independence is associated with high levels of LH-activated adenylyl cyclase and low levels of estradiol receptor. To determine if progesterone secretion is dependent on LH-stimulated adenylyl cyclase during this period of development, ectopic corpora lutea were established in ovariectomized rabbits. Rabbits were injected daily or twice daily with saline or 50, 100, or 150 IU hCG to desensitize LH-responsive adenylyl cyclase. On day 3, 4, 5, or 7, adenylyl cyclase activity was measured in luteal homogenates, and serum progesterone levels were determined by RIA. Basal and LH-stimulated adenylyl cyclase levels rose through day 5 of pseudopregnancy. Daily treatment with 50 or 100 IU hCG did not alter basal activity, but decreased LH-stimulated adenylyl cyclase activity by approximately 50% on day 3, by 80-90% on day 4, and by 90-95% on days 5 and 7. Serum progesterone levels were not different in hCG- and saline-treated rabbits. When LH-stimulated adenylyl cyclase was completely desensitized on days 3 and 4 of pseudopregnancy with twice daily injections of 150 IU hCG, serum progesterone levels were again, not different in saline- and hCG-treated rabbits. These results demonstrate that progesterone production by ectopic corpora lutea is not altered when LH-stimulatable adenylyl cyclase is desensitized and suggest that this early period of luteal development is independent of LH as well as estradiol.

Adenylyl Cyclases↗
PubMed1983

In vitro chemosensitivity of human bladder cancer.

The chemosensitivity of fresh specimens of human transitional cell carcinoma was tested using a novel dye exclusion assay based upon Fast Green staining, cytocentrifugation, and H & E counterstaining. Assays were successful (three or more drugs tested) in 22/24 specimens obtained by cytoscopy and 2/2 specimens obtained by open biopsy. Three of 17 specimens had more than 70% cell kill after a 1-hour exposure to thiotepa (500 micrograms/ml), compared with 10/18 after exposure to mitomycin C (250 micrograms/ml), and 19/19 after exposure to doxorubicin (100 micrograms/ml). There was a trend for specimens with high histologic grades or low control viabilities in short-term culture to be more sensitive to mitomycin C than specimens with low histologic grades or high control viabilities. Comparison of these data with published clinical data suggests that intrinsic chemosensitivity may be the most important determinate of clinical response to intravesical chemotherapy with thiotepa, while drug penetration to the tumor cells may primarily determine clinical response to intravesical doxorubicin. Thiotepa may be most valuable in treating large lesions which are intrinsically sensitive, while doxorubicin may be valuable in nearly all small lesions. Improved drug distribution to tumor sites could improve intravesical therapy with doxorubicin.

Antibiotics, Antineoplastic↗
PubMed1983

Congenital myasthenia gravis in 13 smooth fox terriers.

In 13 Smooth Fox Terriers with a congenital form of myasthenia gravis, clinical signs included intermittent, progressive muscle weakness that became more pronounced with exercise; muscle wasting; megaesophagus; and aspiration pneumonia. Neurologic abnormalities were apparent only during periods of weakness and included inability to retract the fore- and hindlimbs from painful stimuli. A decrement of the compound muscle action potential was evident during repetitive supramaximal nerve stimulation. Intravenous injection of a short-acting cholinesterase inhibitor evoked immediate improvement of clinical and electromyographic signs. Intracellular microelectrode studies of a biopsied external intercostal muscle revealed reduced amplitude of miniature end-plate potentials, as occurs in acquired myasthenia gravis. However, in contrast to acquired myasthenia gravis, antibodies directed against acetylcholine receptors were not demonstrable in serum and were not bound to acetylcholine receptors in muscle. Despite lack of complexing with immunoglobulin, the amount of acetylcholine receptor protein in biopsied external intercostal muscles from 9 affected pups was less than 25% of the amount in 5 unaffected littermates. The latter finding accounted for the reduction in amplitude of miniature end-plate potential and the failure of neuromuscular transmission. Treatment with a long-acting cholinesterase inhibitor in 6 cases resulted in temporary improvement in muscle strength.

Animals↗
PubMed1983

Developmental regulation of 16S acetylcholinesterase and acetylcholine receptors in a mouse muscle cell line.

We have studied the appearance, distribution and regulation of acetylcholinesterase (AChE) and acetylcholine receptors (AChRs) in a mouse skeletal muscle cell line (C2), that was originally isolated and described by Yaffe & Saxel [54]. In culture, cells from this line form spontaneously contracting myotubes, with overshooting action potentials that are TTX-sensitive. After fusion of myoblasts into myotubes, there was a dramatic increase in the amount of both AChE and AChR. Three forms of AChE, distinguished by their sedimentation on sucrose gradients, were synthesized: 4-6S, 10S, and 16S. The 4-6S and 10S forms appeared 1 day after the cells began to fuse, whereas the 16S form appeared only 2 days after fusion began. Maximal levels of the 16S AChE form (25-30% of the total) were obtained by reducing the concentration of horse serum in the fusion medium. Prevention of myoblast fusion by reducing the calcium levels in the medium decreased the total AChE by 70%, and only the 4-6S form was synthesized. Blocking spontaneous contractile activity of the myotubes by tetrodotoxin (TTX) led to a 50% reduction in all three esterase forms. Thus, the 16S, or endplate form of AChE is not specifically regulated by electrical or contractile activity in the C2 cell line. After fusion the number of AChRs increased rapidly for 3-4 days and then stabilized. Receptor clusters, ranging from 10-30 micron in length, appeared 1 day after myoblast fusion began. When cells were grown in medium containing reduced Ca2+, the total number of AChRs was decreased by 20-50%. Reduction of Ca2+ after myotubes and AChR clusters had formed resulted in dispersal of AChR clusters. Inhibition of muscle contractions with TTX did not affect the number of AChRs or their distribution.

Acetylcholinesterase↗
PubMed1983

Characterization and physiological variation of estrogen receptors in rabbit corpora lutea throughout pregnancy and pseudopregnancy: the effect of hysterectomy and sustained estradiol treatment.

Previous studies suggest that regression of the rabbit corpus luteum is associated with a uterine-induced loss of responsiveness to estradiol. To determine if this is due to loss of estrogen receptor, cytoplasmic and nuclear estrogen receptors were measured in pseudopregnant, hysterectomized-pseudopregnant and pregnant rabbits throughout luteal life. Estrogen receptor levels were higher in corpora lutea than in nonluteal tissue and were generally higher in nuclei compared to cytosol. Estrogen receptor levels were low on Day 3, increased 2- to 3-fold by Day 6-8, reached peak levels by Days 8-10, and then gradually decreased in a pattern similar to the pattern of serum progesterone typical of each group. Hysterectomy was not associated with elevated cytoplasmic or nuclear estradiol receptor levels. When hysterectomized rabbits were treated with estradiol-filled Silastic implant on Day 1, nuclear estradiol receptor levels fell by Day 20 to levels seen in untreated hysterectomized rabbits. Despite substantial losses in nuclear estrogen receptor, serum progesterone remained elevated on Days 16 and 20. Thus, the ability of estradiol to maintain serum progesterone in hysterectomized rabbits did not correlate directly with the level of estrogen receptor.

Animals↗
PubMed1983

Alterations in plasma and tissue prostaglandin levels in rabbits during luteal regression.

To determine if ovarian as well as uterine prostaglandin production was associated with luteal regression, tissue and plasma concentrations of prostaglandin F (PGF), prostaglandin E (PGE), 6-keto-PGF1 alpha (6-keto-PGF), and thromboxane B2 (TxB) were measured by radioimmunoassay in uterus, corpora lutea, nonluteal tissue, uterine venous plasma and ovarian venous plasma on Days 8, 12 and 15 of pseudopregnancy in the rabbit. Total prostaglandin levels (PGF + PGE + 6-keto-PGF + TxB) were 4-fold greater in the uterus compared to nonluteal tissue and 8-fold greater than in corpora lutea. Both PGF and PGE levels were increased in uterine tissue on Day 15 compared to Days 8 or 12 (P less than 0.01). The ratio of PGF:PGE was also elevated on Day 15 compared to Days 8 or 12 (P less than 0.05) which suggests that the luteolytic effect of PGF predominates over the possible luteotropic effect of PGE. There were no significant changes in the concentration of TxB or 6-keto-PGF or the ratio of TxB:6-keto-PGF in uterine tissue on any day studied. In nonluteal tissue, PGE was the only PG to vary significantly; PGE levels were elevated (P less than 0.05) on Day 8 of pseudopregnancy compared to Days 12 or 15. Although corpora lutea contain significant quantities of PGF, PGE, TxB and 6-keto-PGF, no alterations in the levels of any of these substances were observed between Days 8, 12 or 15 of pseudopregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Molybdenum cofactor in chlorate-resistant and nitrate reductase-deficient insertion mutants of Escherichia coli.

We examined molybdenum cofactor activity in chlorate-resistant (chl) and nitrate reductase-deficient (nar) insertion mutants and wild-type strains of Escherichia coli K-12. The bacterial molybdenum cofactor was assayed by its ability to restore activity to the cofactor-deficient nitrate reductase found in the nit-1 strain of Neurospora crassa. In the wild-type E. coli strains, molybdenum cofactor was synthesized constitutively and found in both cytoplasmic and membrane fractions. Cofactor was found in two forms: the demolybdo form required additional molybdate in the assay mix for detection, whereas the molybdenum-containing form was active without additional molybdate. The chlA and chlE mutants had no detectable cofactor. The chlB and the narG, narI, narK, and narL (previously designated chlC) strains had cofactor levels similar to those of the wild-type strains, except the chlB strains had two to threefold more membrane-bound cofactor. Cofactor levels in the chlD and chlG strains were sensitive to molybdate. When grown in 1 microM molybdate, the chlD strains had only 15 to 20% of the wild-type levels of the demolybdo and molybdenum-containing forms of the cofactor. In contrast, the chlG strains had near wild-type levels of demolybdo cofactor when grown in 1 microM molybdate, but none of the molybdenum-containing form of the cofactor. Near wild-type levels of both forms of the cofactor were restored to the chlD and chlG strains by growth in 1 mM molybdate.

Chlorates↗
PubMed1983

Cimetidine-associated thrombocytopenia.

A case of thrombocytopenia associated with cimetidine administration in a 65-year-old white female with recurrent adenocarcinoma is reported. Her platelet count fell from 273 000/mm3 to 35 000/mm3 after cimetidine therapy was started. Upon discontinuation of cimetidine, the platelet count increased to 164 000/mm3. Later in her hospital course, the patient again received cimetidine and her platelet count fell to 37 000/mm3. The patient was never leukopenic during her hospitalization. This is the only reported case of thrombocytopenia in the absence of leukopenia that is documented by a rechallenge with cimetidine.

Aged↗
PubMed1983

Treatment of hormone-resistant metastatic carcinoma of the prostate with 5-FU, doxorubicin, and mitomycin (FAM'): a preliminary report.

We treated 19 patients who had hormone-resistant adenocarcinoma of the prostate (stage D-2) with 5-FU, doxorubicin, and mitomycin (FAM'). All patients had extremely poor prognostic factors. Of the 16 patients evaluable for response, 44% had stabilization of disease and 56% had progressive disease. The median survival time for the stable disease group was 48 weeks, whereas that for the nonresponders was 26 weeks. The difference in survival time was statistically significant (P less than 0.002). The FAM' regimen was well-tolerated with minimal nausea, no vomiting, and moderate hematologic toxicity.

Aged↗
PubMed1981

Diffuse histiocytic lymphoma with sclerosis: a clinicopathologic entity frequently causing superior venacaval obstruction.

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to megavoltage radiotherapy alone and relatively resistant to combination chemotherapy.

Adult↗