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Biomedical subjects

M J Higgins

Publications and source records attributed to M J Higgins.

At least 109 records · Page 6Linked to original sources
PubMed1976

The metabolism in vivo and in vitro of plasma low-density lipoprotein from a subject with inherited hypercholesterolaemia.

1. The metabolism in vivo and in vitro of an abnormal low-density lipoprotein (LDL) obtained from a patient with an inherited form of hypercholesterolaemia was compared with that of LDL obtained from a normal subject. 2. The rates of turnover of the apoprotein of the two types of LDL in a normal subject, and their uptake and catabolism by normal lymphocytes in vitro, were similar. 3. It is concluded that the abnormal behaviour of the patient's LDL may not be due to an abnormality in the apoprotein component.

Acacia↗
PubMed1975

Regulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity in type II hyperlipoproteinaemia.

The regulation of 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity in leucocytes was studied in a family with familial type II hyperlipoproteinaemia (WHO classification). The propositus was heterozygous and 16 other members of the family were studied. Leucocytes were isolated by a relatively quick and simple procedure and used for enzyme estimations. The results suggest that measurement of the regulation of this enzyme in leucocytes may be helpful in the diagnosis and management of the condition.

Adolescent↗
PubMed1975

A new type of familial hypercholesterolaemia.

Two members of a family (proband and daughter) with hypercholesterolaemia have an abnormal low-density lipoprotein which fails to suppress the activity of a rate-determining enzyme for cholesterol biosynthesis (3-hydroxy-3-methyl glutaryl-CoA reductase) in leucocytes of the patients and controls. However, the proband's leucocytes are inhibited by lipoproteins from other sources demonstrating that the mechanism for cellular regulation of the enzyme is intact. This mutant lipoprotein may have a role in the production of hypercholesterolaemia.

Adult↗
PubMed1975

Errors in metabolic regulation. A common group of metabolic disorders.

It is postulated that errors in metabolic regulation occur when aminoacid subsitutions or conformational changes occur at allosteric sites on proteins. The cell thus contains its full complement of enzymes, carrier proteins, and receptors, but these proteins do not respond normally to microenvironmental agents such as hormones or activator or inhibitor metabolites. Regulatory errors differ from the classical inborn errors in a number of respects: they can be acquired as well as inherited, when due to defects at allosteric inhibitory sites they lead to loss of regulation of metabolic pathways with oversynthesis of metabolic products without gross accumulation of abnormal intermediates, and they can be treated, in principle, by enzyme inhibitors rather than by enzyme replacement, as for inborn errors.

Adipose Tissue↗
PubMed1973

An investigation into the role of malonyl-coenzyme A in isoprenoid biosynthesis.

1. [(14)C]Malonyl-CoA was incorporated into isoprenoids by cell-free yeast preparations, by preparations from pigeon and rat liver, and by Hevea brasiliensis latex. 2. In agreement with previous reports the incorporation of acetyl-CoA into isoprenoids was not inhibited by avidin and was not stimulated by HCO(3) (-). In a cell-free yeast preparation addition of HCO(3) (-) stimulated the formation of fatty acids from acetyl-CoA and decreased the incorporation into unsaponifiable lipids. 3. The labelling patterns of beta-hydroxy-beta-methylglutaryl-CoA formed from [2-(14)C]- and [1,3-(14)C]-malonyl-CoA in rat and pigeon liver preparations were those that would be expected if malonyl-CoA underwent decarboxylation to acetyl-CoA before incorporation. 4. The labelling pattern of ergosterol formed by cell-free yeast preparations from [2-(14)C]malonyl-CoA was also consistent with decarboxylation of malonyl-CoA before incorporation. 5. The incorporation of [2-(14)C]malonyl-CoA into mevalonate by rat liver preparations was related to the malonyl-CoA decarboxylase activity present in the preparation.

Acetyl Coenzyme A↗
PubMedDate not supplied

Evaluation of plasmapheresis on the removal of tobramycin.

A 26-year-old man with thrombotic thrombocytopenic purpura resulting in respiratory and renal failure was treated with plasmapheresis (PP). Coexisting pulmonary infiltrates were empirically treated as pneumonia with various antibiotics, including vancomycin and tobramycin. The half-life of tobramycin was 6.93 hours. During PP the half-life of tobramycin decreased to 4.47 hours as determined by three random levels. The fraction eliminated due to PP was 35.5% and the fraction cleared by PP was 10.9%. We conclude that PP contributed significantly to the total clearance of tobramycin. The need for supplemental doses must be evaluated in each patient based on post-PP serum concentrations.

Adult↗
PubMedDate not supplied

The pharmacologic basis of the cardiovascular toxicity of minoxidil in the dog.

Minoxidil (MNX), like several other vasoactive drugs, causes cardiovascular toxicity in dogs by undetermined mechanisms. We studied the mechanism of cardiovascular toxicity of MNX [an adenosine triphosphate (ATP)-sensitive potassium channel opener] by blocking its pharmacologic effects with glyburide (an ATP-sensitive potassium channel blocker) in groups of 5 female beagle dogs treated orally for 2 days with 1.0 mg/kg/day of MNX alone or with glyburide given in 5 or 6 divided doses of 300 mg/kg at 2 hr before and after each dose of MNX and at 3-6-hr intervals thereafter. A third group of 5 dogs received glyburide alone in the same dosing regimen as in the combination group. Mean arterial pressure (MAP), heart rate (HR), the pharmacokinetics of MNX, and gross and microscopic changes in the heart were evaluated. Glyburide did not influence the pharmacokinetics of MNX but prevented or markedly attenuated the MNX-induced cardiovascular lesions (right atrial hemorrhagic lesions, subendocardial necrosis, or coronary arteritis) occurred in dogs whose MNX-induced hemodynamic effects were effectively blocked by glyburide. In conclusion, the cardiovascular toxicity of MNX in dogs is not caused by a direct toxic effect of MNX on the heart but apparently is related to the exaggerated pharmacologic/profound hemodynamic effects it elicits in the dog.

Animals↗
PubMedDate not supplied

Evaluation of plasmapheresis in the treatment of an acute overdose of carbamazepine.

OBJECTIVE: To report the use of plasmapheresis in the treatment of an acute overdose of carbamazepine. CASE SUMMARY: A 21-year-old black man was admitted unresponsive and combative following a carbamazepine overdose. The total body load of carbamazepine was approximated at 5.91 g using an assumed volume of distribution of 1.4 L/kg. The patient underwent three plasmapheresis treatments. A total of only 335.82 mg of carbamazepine was removed by this process. DISCUSSION: Case reports in the literature were reviewed and compared. Carbamazepine concentrations lack correlation with the clinical outcome. Our patient's symptoms were consistent with the Weaver classification system. Carbamazepine clearance increased by almost 70 percent above its natural clearance during plasmapheresis. However, a significant rebound effect was observed after plasmapheresis: 40.1 percent after the first and 18.3 percent after the second treatment. CONCLUSIONS: Plasmapheresis did not seem to have a great impact on the patient's clinical status. Under the circumstances we find it extremely difficult to recommend plasmapheresis in the treatment of an acute overdose of carbamazepine.

Adult↗
PubMedDate not supplied

Anatomical methods in the study of cardiovascular pathology: a refined technique.

A refined technique is described for the anatomical study of the heart and coronary arteries after perfusion with agar-barium sulfate contrast medium. The method includes dissection and isolation of the perfused coronary arteries with sequential cross-sectioning and radiography of intact and cross-sectioned vessels. This technique allows better evaluation of the extent of cross-luminal narrowing and improved selection of myocardium for histologic sectioning. This affords better correlation of autopsy and clinical findings than conventional methods and permits easier retrieval of data and better standardization of results for use in pathological studies.

Angiography↗
PubMedDate not supplied

The use of monoclonal antibodies in the diagnosis of peripheral T-cell lymphomas.

Sixteen cases of peripheral T-cell lymphomas are described which are characterized immunologically by various methods including the use of monoclonal antibodies (Ab) to a variety of lymphocyte antigens. Seven cases were classified as helper/inducer and two as suppressor/cytotoxic phenotype. Four were considered T-cell, not otherwise specified, owing to lack of expression of subset phenotypic markers. Three cases were diagnosed prior to the advent of monoclonal Ab methods and were classified as being of T-cell origin by the E-rosette technique. In none of the cases was monotypic surface immunoglobulin or B-cell antigens expressed. The freeze-dried technique to prepare tissues for immunoperoxidase studies was found to be advantageous. The benefits and limitations of monoclonal Ab in the diagnosis of T-cell lymphomas are discussed.

Antibodies, Monoclonal↗