PubMed HealthSearch

Biomedical subjects

M H Brooks

Publications and source records attributed to M H Brooks.

At least 19 recordsLinked to original sources

Thiophosphorylated proteins in chromaffin cells are chromaffin vesicle matrix proteins.

Bovine adrenal chromaffin cells were incubated with inorganic thiophosphate, using a protocol similar to experiments with inorganic phosphate, in order to determine the source of previously observed thiophosphoproteins. Incubation of cultured cells with [35S]thiophosphate resulted in its incorporation into cell constituents within 2 min. SDS-PAGE of the treated cells showed incorporation of label into a broad 97-121 kDa band that was evident after 5 min of treatment and increased progressively to the 40 min exposure limit. Monolayers of chronically treated cells were fractionated into subcellular constituents. The only particulate fraction containing radiolabelled proteins was the chromaffin vesicle fraction. Two-dimensional electrophoresis of the treated cells and isolated chromaffin vesicles showed a majority of proteins in the acidic region of the first dimension gel. A fluorogram of the gel revealed two regions of radiolabelled proteins at acidic and neutral regions of the 2-D gel. These were within the boundaries of the 97-121 kDa band. The thiophosphorylated proteins were released as soluble proteins upon osmotic or freeze-thaw lysis of the vesicles. Chromaffin vesicles isolated from either cultured cells or adrenal medulla tissue were energized by 2 mM ATP but not by the analog adenosine 5'-O-(3-thiotriphosphate). The 97-121 kDa proteins in intact or lysed vesicles prepared from adrenal medulla tissue were not thiophosphorylated by either inorganic thiophosphate or adenosine 5'-O-(3-thiotriphosphate) in the presence or absence of energization by ATP. Nearly complete loss of radiolabel from matrix proteins treated with chondroitinase ABC suggests that it is a component of vesicle proteolgycans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Inorganic thiophosphate effects on chromaffin cell structure and function.

The effect was determined of replacing medium inorganic phosphate with thiophosphate on the structure and function of cultured bovine chromaffin cells. Cell cultures were incubated in normal medium containing fetal bovine serum, phosphate free medium or similar medium supplemented with inorganic phosphate or thiophosphate. In contrast to the other media, cells cultured with thiophosphate medium for 3-4 days showed seriously compromised structure and functions. The cells lost 75% of their catecholamine content and their ability to secrete remaining catecholamines in response to nicotine stimulation. Radiolabelled thiophosphate was rapidly taken up by the cells and, in long-term experiments, was incorporated largely into a 97-121 kDa protein band on SDS-PAGE. Additional minor bands were found to a lesser, variable extent. Transmission electron micrographs of cells treated with thiophosphate showed extensive depletion of chromaffin vesicles and disruption of mitochondria, suggesting that the functional damage noted with these cells could be associated with damage to mitochondria. Analysis of general cell metabolic activity by conversion of the dye (3-[3,4-dimethylthiazol-2-yl]-3,5-diphenyltetrazolium bromide) to its formazan derivative indicated increased metabolic activity at early stages of exposure to thiophosphate followed by a decline with continued exposure, supporting the argument for an overall depression of cell metabolism. Uptake of the dye neutral red, which is avidly accumulated by chromaffin cells, was also reduced for cells exposed to thiophosphate. The data suggest that thiophosphate enters chromaffin cells and disrupts energy dependent cell functions, including catecholamine storage and secretion.

Animals

Inhibition of existing denitrification enzyme activity by chloramphenicol.

Chloramphenicol completely inhibited the activity of existing denitrification enzymes in acetylene-block incubations with (i) sediments from a nitrate-contaminated aquifer and (ii) a continuous culture of denitrifying groundwater bacteria. Control flasks with no antibiotic produced significant amounts of nitrous oxide in the same time period. Amendment with chloramphenicol after nitrous oxide production had begun resulted in a significant decrease in the rate of nitrous oxide production. Chloramphenicol also decreased (greater than 50%) the activity of existing denitrification enzymes in pure cultures of Pseudomonas denitrificans that were harvested during log-phase growth and maintained for 2 weeks in a starvation medium lacking electron donor. Short-term time courses of nitrate consumption and nitrous oxide production in the presence of acetylene with P. denitrificans undergoing carbon starvation were performed under optimal conditions designed to mimic denitrification enzyme activity assays used with soils. Time courses were linear for both chloramphenicol and control flasks, and rate estimates for the two treatments were significantly different at the 95% confidence level. Complete or partial inhibition of existing enzyme activity is not consistent with the current understanding of the mode of action of chloramphenicol or current practice, in which the compound is frequently employed to inhibit de novo protein synthesis during the course of microbial activity assays. The results of this study demonstrate that chloramphenicol amendment can inhibit the activity of existing denitrification enzymes and suggest that caution is needed in the design and interpretation of denitrification activity assays in which chloramphenicol is used to prevent new protein synthesis.

Carbon

Fever in pheochromocytoma.

BACKGROUND: Fever is an infrequently reported finding in patients with pheochromocytoma. Fever in patients with pheochromocytoma may be caused by the tumor, an infection or other factors, each of which will dictate different treatment strategies. METHODS: To determine the incidence, cause, and significance of fever in patients with pheochromocytoma, we reviewed the medical records of 50 hospitalizations of 48 patients. Patients were categorized by the presence or absence of fever. Body temperature elevation, duration of hospitalization in the period prior to surgery or death, age, sex, race, other conditions that could have been responsible for the febrile episode (comorbid events), location, gross and microscopic features of the tumors, and plasma and urine hormone levels were tabulated. The results were compared between the two groups of patients. RESULTS: Fever was present in 14 (28%) of 50 hospitalizations, seven patients (50%) of whom had pheochromocytoma multisystem crisis. Patients with fever and pheochromocytoma were significantly more likely to have a comorbid event, larger tumor, necrosis within the tumor, higher urinary metanephrine levels, longer duration of hospitalization prior to surgery, and to be non-white. Comorbid events included both infectious and noninfectious potential causes of fever. CONCLUSIONS: Fever is common in patients with pheochromocytoma. The causes may be multifactorial and often include an associated illness. A thorough search for coexisting disease is indicated. While fever may prolong hospitalization, it does not portend a disastrous outcome.

Adrenal Gland Neoplasms

Follicular cell predominance in the cytologic examination of dominant thyroid nodules indicates a sixty percent incidence of neoplasia.

The interpretation of aspiration cytologic smears that contain a predominance of follicular components often presents a dilemma to the clinician who is treating a patient who has a dominant thyroid nodule, especially when thyroid-stimulating hormone suppression does not produce any significant involution of the dominant nodule. We reviewed a consecutive series of 555 fine-needle aspiration cytologic examinations of dominant thyroid nodules. All specimens that contained colloid or follicular cells mixed with lymphocytes or Hürthle cells were excluded from this review. Additionally, nine aspirates contained degenerated follicular cells with insufficient material for cytologic diagnosis. The remaining 76 specimens contained a predominance of follicular cells: 27 specimens were interpreted as containing "normal" follicular cells, and the remaining 49 specimens were read as "atypical" follicular cells. Histopathologic examination of the resected specimens indicated a 60% incidence of neoplasia (30% carcinoma, 30% adenoma) in which the aspiration cytologic study was interpreted as "normal" follicular cells. On the other hand, a 63% incidence of neoplasia (27% carcinoma, 36% adenoma) occurred in which the cytologic study was read as "atypical." In conclusion, aspirates showing a predominance of follicular cells, whether "normal" or "atypical" indicate a 60% incidence of neoplasia in dominant thyroid nodules that do not decrease significantly in size with thyroid-stimulating hormone suppression.

Adenocarcinoma

Long-term results of adrenal autotransplantation in Cushing's disease.

Many advances have been made in the diagnosis and treatment of patients with Cushing's disease. Currently, partial or total transsphenoidal resection of the pituitary gland is the surgical approach favored by many authorities, with cure rates of 80% to 90% reported for selected patients. However, long-term follow-up is still needed for this treatment modality, and recurrence rates of up to 50% have been reported. In addition, less favorable results are seen with this approach when there is recurrence after initial transsphenoidal surgery or when there is not a single microadenoma responsible for the disease of the pituitary gland. We report a series of 14 patients who were treated with bilateral adrenalectomy and autotransplantation. Follow-up is 4 to 14 years. Four patients show iodocholesterol uptake at the site of autotransplantation. Of these, three patients have been weaned from cortisone for 12, 10, and 2 years. The fourth patient, after being weaned from all medications, underwent partial resection of a hyperfunctioning autotransplant and currently, 7 years after the original operation, is being weaned from cortisone. A fifth patient was weaned to a reduced dose of cortisone for 8.5 years, but the dose was recently increased. There is no evidence of Nelson's syndrome in any of these patients with clinical evidence of functioning autotransplants. We believe that bilateral adrenalectomy with autotransplantation still plays an important role in the long-term management of selected cases of Cushing's disease and that autotransplantation, when successful, results in few complications and allows long-term freedom from exogenous steroid medication.

Adolescent

Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycemia.

We describe a case of recurrent hypoglycemia apparently caused by secretion of insulin-like growth factor II (IGF-II) by a leiomyosarcoma. A 67-year-old woman presented with recurrent severe hypoglycemia and a large mass in the thorax. During hypoglycemia, plasma cortisol was elevated, but insulin and growth hormone levels were low. After resection of a large leiomyosarcoma, the hypoglycemia resolved. After an eight-year remission, both the tumor and symptomatic hypoglycemia recurred. During a second operation a second large tumor was removed, with relief of the patient's hypoglycemia. The tumor contained high concentrations of IGF-II mRNA and 2100 ng of IGF-II immunoreactive peptide per gram. Filtration through a BioGel P-60 gel column established that 77 percent of the IGF-II was present as a larger molecule, demonstrating incomplete processing of the pro-IGF-II peptides. A similar fraction of high-molecular-weight IGF-II was present in the serum, indicating that the tumor was the chief source of IGF-II. The high-molecular-weight IGF-II found in both the tumor and serum was fully reactive with the IGF-II receptor. Radioimmunoassay showed that the concentrations of insulin-like growth factor I (IGF-I) in tumor and serum were low, suggesting feedback inhibition of growth hormone secretion by IGF-II. Eight months after reoperation, plasma concentrations of IGF-I and IGF-II were normal, and high-molecular-weight IGF-II was virtually undetectable. We conclude that the most likely cause of this patient's recurrent hypoglycemia was IGF-II produced by the leiomyosarcoma.

Aged

Family practitioner participation in routine antenatal care in Israel: what hospital gynaecologists think.

Antenatal care by family practitioners in Israel is unusual. Patient demand, increasing tendency to specialization, high doctor to patient ratio and historical reasons all partly explain the phenomenon. A postal survey of the heads of 34 delivery units was carried out to find out their attitude towards such care and to a proposed follow-up card. Twenty per cent of the gynaecologists surveyed were in favour of antenatal care by family practitioners, a higher figure than the author had anticipated. The role of the family practitioner in antenatal care is discussed.

Attitude of Health Personnel

Plasma catecholamine changes during excision of pheochromocytoma.

Sequential changes in plasma norepinephrine (NE) and epinephrine (EPI) concentration were correlated with changes in blood pressure and cardiac rate in 14 patients undergoing surgery because of pheochromocytoma. All patients had elevated preoperative plasma catecholamine levels that increased during induction of anesthesia, intubation, and skin incision, but mean values did not become significantly higher than preoperative values until tumor manipulation. Episodes of hypertension were associated with increased plasma catecholamine levels, and plasma catecholamine levels and blood pressure decreased dramatically after tumor resection. NE and EPI were usually secreted simultaneously, but release of either NE or EPI alone occurred on some occasions. There were marked variations in the concentration ratio of NE to EPI in plasma at different periods of observation, which suggests that pheochromocytomas release varying amounts of catecholamines in a random fashion. Studies of the effect of the duration of preoperative preparation on intraoperative blood pressure, pulse rate, and cardiac arrhythmias failed to demonstrate that treatment for 14 days or longer was more effective than treatment for 4 to 7 days. Neither the brief nor the prolonged period of therapy prevented development of severe hypertension during tumor manipulation.

Adolescent

Plasmapheresis: an adjunct to medical management of severe hyperthyroidism.

A woman with hyperthyroidism and myasthenia gravis developed respiratory failure in association with radiation-induced thyroiditis. Treatment with steroids, propylthiouracil, propranolol, iodine, and plasmapheresis was associated with dramatic reduction in serum triiodothyronine (T3), serum thyroxine (T4), and thyroglobulin levels and prompt recovery of the patient. The medications that this patient received have been shown to cause an abrupt decline in serum T3 levels with little or no effect on the serum T4 concentration. The 56% decline in serum T4 observed in this patient during the first 24 hours of therapy suggests that plasmapheresis may be a useful adjunct to medical therapy in selected patients with severe hyperthyroidism.

Adult

Pontine hemorrhage in a patient with pheochromocytoma.

A 24-year-old woman with a two-year history of hypertension was hospitalized for coma and quadriplegia secondary to pontine hemorrhage. A seven-year history of intermittent severe headaches, diaphoresis, and anxiety together with persistent severe hypertension led to the diagnosis of pheochromocytoma. This unusual but devastating manifestation of pheochromocytoma illustrates the importance of excluding remedial forms of hypertension in young patients before initiating antihypertensive therapy.

Adrenal Gland Neoplasms

Intractable hypoglycemia in a patient with renal failure.

A patient with chronic renal failure developed intractable hypoglycemia after 2 1/2 years of dialysis. Metabolic studies did not suggest that malnutrition, substrate limitation, hormone deficiency, or insulin excess were responsible for the low blood glucose level. Impaired gluconeogenesis may have been an important factor, but studies in this patient suggest that enhanced glucose utilization may also play a role in the pathogenesis of hypoglycemia in renal failure.

Adult

The continued importance of adrenalectomy in the treatment of Cushing's disease.

Eighteen patients with pituitary-dependent Cushing's disease have been treated during a ten-year period. Eleven of these received a total of 14 alternative forms of therapy in an attempt to control the clinical manifestations of Cushing's disease prior to adrenalectomy. However, no substantial improvement was noted in these patients, who included four receiving conventional pituitary irradiation, five receiving cyproheptadine, two receiving mitotane, and one each receiving metyrapone and phenytoin. One patient had an attempted transsphenoidal hypophysectomy that could not be accomplished because of hemorrhage. A complete remission of the signs, symptoms, and laboratory abnormalities of Cushing's disease occurred in all 18 patients following bilateral adrenalectomy. There was no operative mortality and morbidity was minimal. This experience confirms that bilateral adrenalectomy is a rapid, safe, and permanent means of reversing hypercortisolism and that it should remain an integral part of the treatment of Cushing's disease.

Adolescent