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Biomedical subjects

M Brooks

Publications and source records attributed to M Brooks.

At least 73 records · Page 4Linked to original sources
PubMed1985

Protein thiophosphorylation associated with secretory inhibition in permeabilized chromaffin cells.

Permeabilized cells treated with the adenosine triphosphate analog, [35S]adenosine-5'-0-(3-thiotriphosphate) ([gamma-35S]ATP), showed thiophosphorylation of a small number of cellular proteins. A 54 kilodalton (kDa) protein was heavily thiophosphorylated in unstimulated control cells and a 43 kilodalton protein was more heavily thiophosphorylated in calcium stimulated cells. Intact cells incorporated 35S into a series of higher molecular weight proteins. Stimulation of prelabelled, permeabilized cells resulted in a loss of 35S from the cells over a 20 min period. Treatment of permeabilized cells with ATP gamma S inhibited secretion and 35S incorporation into the cells. Pretreatment with ATP gamma S resulted in subsequent inhibition of both secretion and the ability of the cells to incorporate 35S from [gamma-35S]ATP. These results indicate that the sites normally available for phosphorylation were inactivated by thiophosphorylation and were unavailable to participate in the secretory process. The inhibition of secretion associated with thiophosphorylation of these proteins suggests that they may play a role in the control of secretion by chromaffin cells.

Adenosine Triphosphate↗
PubMed1984

Thiophosphorylation prevents catecholamine secretion by chemically skinned chromaffin cells.

Skinned cells treated with the adenosine triphosphate analog, adenosine-5'-0-(3-thiotriphosphate) showed calcium-dependent thiophosphorylation of cellular constituents. Catecholamine secretion was inhibited when the analog was used as the substrate to promote secretion. The attenuation of secretion was proportional to the percentage of the analog in mixtures with adenosine triphosphate. Moreover, cells treated with the analog were subsequently unable to secrete when presented with MgATP, their normal substrate, indicating that the secretory systems was locked in the thiophosphorylated state. We hypothesize that phosphorylation is the calcium-dependent step required to prime the secretory system for secretion while dephosphorylation is the event required for exocytosis.

Adenosine Triphosphate↗
PubMed1984

Isozyme profiles of oval cells, parenchymal cells, and biliary cells isolated by centrifugal elutriation from normal and preneoplastic livers.

The fetal liver isozymes aldolase A and pyruvate kinase K increase in livers of adult rats fed a choline deficient-diet containing 0.1% ethionine. Oval cells isolated by centrifugal elutriation from preneoplastic livers of animals receiving the carcinogenic diet contained these fetal forms as well as fetal-adult isozyme hybrids. In contrast, parenchymal cells isolated from the livers of these animals had only aldolase B and pyruvate kinase L, the same isozymes present in parenchymal cells of normal adult rats. Liver homogenates from rats receiving the carcinogenic diet contain lactate dehydrogenase (LDH) 1, LDH 2, and LDH 3 in addition to LDH 4 and LDH 5, which are the forms detected in normal liver homogenates. LDH 1, LDH 2, and LDH 3 are present in oval cells of preneoplastic livers and in biliary epithelial cells of normal livers, but not in parenchymal cells isolated from normal and preneoplastic livers. Cells of biliary epithelium from normal livers also contain aldolase A and pyruvate kinase K, but not the fetal-adult isozymes present in oval cell populations. The results indicate that, in animals receiving this carcinogenic diet, isozyme alterations associated with neoplasia result from the proliferation of a new cell population which contains these enzymes and not from "dedifferentiation" of mature hepatocytes. Furthermore, the data suggest that this new cell population may include a liver stem cell compartment containing cells in transitional states of differentiation.

Animals↗
PubMed1983

The use of drugs to dissect the pathway for secretion of the glycoprotein hormone chorionic gonadotropin by cultured human trophoblastic cells.

Agents that affect intracellular cation and pH gradients and inhibit energy production have been tested for their ability to modulate the processing and secretion of the free alpha subunit and the alpha beta dimer of human chorionic gonadotropin (hCG) by cultured human trophoblastic cells (JAR). Incubation of JAR cells with monensin or nigericin, monovalent cation ionophores that produce equilibration of Na+ and K+ across cellular membranes, dicyclohexylcarbodiimide, an agent that inhibits intracellular membrane ATPases, and methylamine, which neutralizes intracellular pH gradients, produced similar effects on hCG processing and secretion. All these agents inhibited the processing of the asparagine-linked oligosaccharide chains of free alpha subunit and the alpha and beta subunits contained in the hCG dimer. Moreover, after treatment of JAR cells with these agents, there was an intracellular accumulation of precursor forms and an inhibition of secretion of "mature" forms of hCG. Monensin affected the processing and secretion of hCG subunits differently at different concentrations. At 5 X 10(-7) M, monensin inhibited the processing of the asparagine-linked oligosaccharides of hCG without altering the rate-limiting step in the secretory pathway or blocking hCG secretion. The intracellular hCG subunit precursors in both control and monensin-treated cells contained a similar array of high mannose oligosaccharides, predominantly of the Man8GlcNAc2 and Man9GlcNAc2 types. However, monensin-treated cells secreted hCG subunits that contained endo H-sensitive oligosaccharides of the high mannose (mostly Man5GlcNAc2) and hybrid types rather than the endo H-resistant complex chains synthesized by control cells. Nevertheless, a full complement of serine-linked oligosaccharides was added to the hCG-beta subunit in monensin-treated cells. These results indicate that the intracellular movement of hCG from the rough endoplasmic reticulum to the cell surface was not inhibited by monensin at a concentration that impaired Golgi-localized steps in the processing of asparagine-linked oligosaccharides. At 5 X 10(-6) M, monensin significantly inhibited secretion of hCG and created a new rate-limiting step in the processing pathway. hCG subunits bearing Man5GlcNAc2 units accumulated intracellularly, suggesting that the equilibration of intracellular Na+/K+ pools blocked oligosaccharide processing at an intra-Golgi point, perhaps by inhibiting movement of the glycoprotein hormone from the "cis" to the "trans" Golgi compartment. Since the other drugs mentioned above produced similar effects on hCG processing and secretion, it appears that maintenance of intracellular cation and pH gradients is necessary for the intra-Golgi transport of glycoprotein hormones.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcimycin↗
PubMed1981

Altered form of placental alkaline phosphatase produced by JAR choriocarcinoma cells in culture.

The alkaline phosphatase activity expressed by JAR choriocarcinoma cells was compared to the placental isoenzyme of human alkaline phosphatase by several criteria. JAR cell alkaline phosphatase was similar to the placental isoenzyme with respect to heat and urea stability and sensitivity to most inhibitors, but it differed significantly from placental alkaline phosphatase in its sensitivity to L-phenylalanylglycylglycine. In contrast to the serum form of placental alkaline phosphatase, the JAR cell enzyme was highly hydrophobic as determined by octyl agarose chromatography and appeared to be larger than the placental isoenzyme based on gel filtration and polyacrylamide gel electrophoresis. The slowly migrating hydrophobic JAR cell activity could be converted into a fast-migrating hydrophilic form similar to the serum placental isoenzyme by treatment with trypsin-like proteases. Conversion to the hydrophilic form was accompanied by a decrease in subunit molecular weight from 68,000 to 66,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 33P-labeled enzyme. Peptide mapping of the 33P-labeled molecules by limited proteolysis in the presence of sodium dodecyl sulfate showed JAR cell alkaline phosphatase to be closely related to the placental isoenzyme with respect to primary structure. However, placental alkaline phosphatase appeared to be richer in sialic acid residues than was the JAR cell enzyme. We conclude that JAR cells produce a form of placental alkaline phosphatase that contains a hydrophobic region not associated with the free serum enzyme and that the tumor cell enzyme is modified or processed differently than is the enzyme found in the term placenta.

Alkaline Phosphatase↗
PubMed1981

Liver abscess.

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Adolescent↗
PubMed1981

Hyperparathyroid crisis. Successful treatment of ten comatose patients.

Hyperparathyroid crisis is a rare disease manifested by elevated serum calcium, weakness, nausea and vomiting, altered states of consciousness, and elevated circulating parathormone. This hypercalcemic state is noted for a frequently acute presentation and associated high mortality rate, approaching 60% in some series. Ten patients in parathyroid crisis were observed in a consecutive personal series of 325 cases of operatively proved hyperparthyroidism. All 10 patients were successfully treated. Each patient remained or lapsed into persistent coma despite extensive medical management and normalization of serum calcium in some instances. An emergency parathyroidectomy was performed in all cases. Reversal of the comatose state was noted in all patients within 24 hours, followed by gradual normalization of serum calcium. Serum calcium ranged from 15 to 19.6 mg/dl. The blood urea nitrogen level was elevated in six patients. A single adenoma was found in nine patients and multiglandular disease involving the neck and the mediastinum in one. All patients survived. The successful treatment of this disease demands prompt and accurate diagnosis coupled with vigorous medical therapy and emergency parathyroidectomy if the patient's status continues to deteriorate.

Acute Disease↗
PubMed1981

Adverse drug reactions.

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Drug-Related Side Effects and Adverse Reactions↗
PubMed1980

Estramustine phosphate: plasma concentrations of its metabolites following oral administration to man, rat and dog.

Estramustine phosphate, a nitrogen mustard derivative of estradiol used for the treatment of advanced prostatic cancer, was administered orally to man, rat and dog and the plasma concentrations of its unconjugated metabolites were determined by high performance liquid chromatography. In all species the drug was rapidly and completely dephosphorylated prior to reaching the peripheral circulation. In man and the rat, the 17-keto analogue of estramustine (estromustine) was the mamor metabolite found in plasma with considerably lesser amounts of estramustine itself. In the dog, significant concentrations of both estramustine and estromustine were present. Highly elevated levels of both estrone and estradiol, as a result of cleavage of the nitrogen mustard from the steroid, were observed in all species. Chronic administration of therapeutic doses of estramustine phosphate to man did not result in any apparent accumulation of circulating metabolites. The study suggests that the metabolite, estromustine, in addition to estramustine, may play an important role in the therapeutic efficacy of estramustine phosphate.

Administration, Oral↗
PubMed1980

Radioimmunoassay of thyroxine in 10 microliters of serum, with use of aggregated antithyroxine antibodies.

We describe a sensitive radioimmunoassay for rapidly determining the concentration of thyroxine in 10 microL of human serum. Aggregated antithyroxine antibodies are used to separate bound and free hormone. This speeds the assay and economizes on reagents without loss of sensitivity, specificity, or precision. Results for normal subjects and patients with thyroid disease agree well with those obtained by other, well-established techniques.

Antibodies↗
PubMed1979

Nerve entrapments associated with postmastectomy lymphedema.

Ninety females underwent mastectomy for breast cancer and were thereafter investigated to determine whether nerve entrapments were responsible for some of the disabling symptoms in their arms. The majority of these patients suffered from fullness (edema), numbness, paraesthesia, weakness and pain of the arm on the mastecotmized side. Lymphedema of varying degrees found in 50% of these patients was associated with brachial plexus entrapment and carpal tunnel syndrome (CTS). 28% of the patients has CTS, and 28% suffered from brachial plexus entrapment of the arm on the mastecotmized side, as compared with 8% and 5%, respectively, on the nonoperated side. 12% of the patients suffered from both types of entrapment. Thus we consider that brachial plexus entrapment and carpal tunnel syndrome should be added to the list of complications following mastectomy, with lymphedema playing an active part in their development.

Adult↗
PubMed1979

Alimentary tract complications after renal transplantation.

A computer analysis of post renal transplantation gastrointestinal problems was performed to identify important associated clinical factors. Thirty-seven per cent of all transplant recipients developed one or more significant problems. Hemorrhage, nondiverticular intestinal perforation, and esophagitis occurred most frequently in hospitalized patients. Pancreatitis, diverticulitis, and gastroduodenal perforation occurred characteristically in long-term survivors with well functioning allografts. Eleven of 32 HLA identical recipients treated with maintenance corticosteroids during stable kidney function developed gastrointestinal disease while only one of 13 HLA identical recipients not given maintenance steroids developed a problem, which strongly suggests a causal role for steroids in the development of late complications. The association of preexisting peptic ulcer and diverticular disease with hemorrhage and perforation supports previous recommendations that documented peptic ulcer disease or diverticulitis should be corrected surgically prior to transplantation.

Adolescent↗