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Biomedical subjects

M Hooper

Publications and source records attributed to M Hooper.

At least 37 records · Page 2Linked to original sources

Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells.

Specific genes can be inactivated or mutated in the mouse germ line. The phenotypic consequences of the mutation can provide pivotal information on the function of the gene in development and maintenance of the mammalian organism. The procedure entails homologous recombination in embryonic stem cells, which, on fusion to recipient blastocysts, give rise to chimaeric mice that can transmit the mutant gene to their offspring. Inbreeding can then yield mice carrying the mutation in both alleles allowing the phenotypic analysis of recessive mutations. In addition to mice lacking a particular gene function, cell lines carrying null alleles of normally expressed genes can be instrumental in assessing the function of the gene. These cell lines can either be obtained from homozygous animals or, should the mutation be lethal early in embryonic development, be generated by consecutive inactivation of both alleles by homologous recombination in cultured cells. Here we illustrate the feasibility of this latter approach by the efficient consecutive inactivation of both alleles of the pim-1 proto-oncogene in embryonic stem cells.

Animals↗

Ilio-tibial band friction syndrome--a common injury.

Ilio-tibial band syndrome is a common sports injury in runners that is easy to recognise and treat. Unfortunately, it is infrequently diagnosed so that much unnecessary morbidity from the condition exists.

Athletic Injuries↗

Dexamethasone concentrations and the dexamethasone suppression test in psychiatric disorders.

The dexamethasone suppression test (DST) has been widely used in psychiatry as a laboratory aid for the diagnosis of endogenous depression; failure to suppress serum cortisol levels is interpreted as confirming a clinical diagnosis of endogenous depression. We found that serum dexamethasone concentrations in this test vary widely and are determinants of the DST response: non-suppression of serum cortisol levels is associated with low serum dexamethasone concentrations, and suppression is associated with high concentrations.

Adjustment Disorders↗

Dynamics of interaction between complement-fixing antibody/dsDNA immune complexes and erythrocytes. In vitro studies and potential general applications to clinical immune complex testing.

Soluble antibody/3H-double-stranded PM2 DNA (dsDNA) immune complexes were briefly opsonized with complement and then allowed to bind to human erythrocytes (via complement receptors). The cells were washed and subsequently a volume of autologous blood in a variety of media was added, and the release of the bound immune complexes from the erythrocytes was studied as a function of temperature and time. After 1-2 h, the majority of the bound immune complexes were not released into the serum during blood clotting at either 37 degrees C or room temperature, but there was a considerably greater release of the immune complexes into the plasma of blood that was anticoagulated with EDTA. Similar results were obtained using various conditions of opsonization and also using complexes that contained lower molecular weight dsDNA. Thus, the kinetics of release of these antibody/dsDNA immune complexes differed substantially from the kinetics of release of antibody/bovine serum albumin complexes that was reported by others. Studies using the solution phase C1q immune complex binding assay confirmed that in approximately half of the SLE samples that were positive for immune complexes, there was a significantly higher level of detectable immune complexes in plasma vs. serum. Freshly drawn erythrocytes from some SLE patients exhibiting this plasma/serum discrepancy had IgG antigen on their surface that was released by incubation in EDTA plasma. Thus, the higher levels of immune complexes observed in EDTA plasma vs. serum using the C1q assay may often reflect the existence of immune complexes circulating in vivo bound to erythrocytes.

Antigen-Antibody Complex↗

Functional evaluation of the spinal accessory nerve after neck dissection.

The pain and dysfunction associated with a loss of innervation by the spinal accessory nerve has motivated surgeons to modify the classic radical neck dissection. A prospective study of 109 patients who underwent either a radical neck dissection or a modification of it with preservation of the spinal accessory nerve revealed that those patients in whom the nerve, muscle, and vein were preserved had less dysfunction (30 percent) than those with nerve preservation only (50 percent) or classic radical neck dissection (60 percent). In addition, even when the functional disability was the same, there was less associated pain with nerve-sparing procedures. Furthermore, a large group of patients (40 percent) who underwent classic radical neck dissection had minimal disability. Given these results, a prospective study of recurrence data in these patients is indicated.

Accessory Nerve↗

Increased inhibitory action against adenosine 5'-triphosphate in the isolated taenia of the guinea-pig caecum by substitution in the A-ring of 2-phenylisatogen.

1 The ability of a series of 17 isatogen derivatives to relax smooth muscle, inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in isolated mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 Substitution in the 4- and 7-positions of the A-ring gave compounds that were strong inhibitors of mitochondrial ATP synthesis and potent, non-specific smooth muscle relaxants. The compounds also possessed ATP-receptor blocking activity. 3 Substitution in the 5- and 6-positions of the A-ring decreased both the relaxant effect on smooth muscle and inhibition of ATP synthesis, whilst enhancing ATP-receptor antagonism. 4 In a series of 6-substituted 2-phenylisatogens, 6-methoxy-2-phenylisatogen was the most effective ATP-receptor antagonist. This compound also showed the greatest separation of the desired pharmacological activity (ATP-receptor blockade) from the other two activities (smooth muscle relaxation and inhibition of mitochondrial ATP synthesis).

Adenosine Triphosphate↗

Radiation-associated thyroid tumors: extent of operation and pathology technique influence the apparent incidence of carcinoma.

A prospective study and follow-up program of 2,118 patients with prior low-dose head and neck irradiation, entered into a thyroid screening project, allowed us to examine how the extent of operation and pathology technique influenced the incidence of thyroid carcinoma. Patients with palpable nodular thyroid disease were referred to their physicians with a recommendation for surgery: 107 patients had thyroid surgery in community hospitals (CHs) where enucleation of the nodule or lobectomy was the usual operation, and 29 patients had surgery at Milwaukee County Medical Complex (MCMC) where near-total thyroidectomy was routine. Lymph nodes were sampled in 69% of MCMC operations but in only 16% of CH operations. The pathologist's usual method at MCMC was to submit the total surgical specimen and to do serial sections. Less than total specimen examination and random sections typically were done in community hospitals. The mean age and sex ratio of the patients and size of thyroid lesions in the two groups were not different. Cancer was found in 59% (17/29) of patients who underwent operation at MCMC, while only 21% (22/107) of patients who underwent operation in CHs were found to have carcinoma (P less than 0.001). Surprisingly, there was nearly uniform agreement (99%) in the diagnoses made by MCMC and CH pathologists, and the incidence of microscopic foci of carcinoma was similar in both groups. We conclude that the incidence of thyroid carcinoma found in patients with prior head and neck irradiation who have had operation for thyroid nodules is related to the extent of thyroidectomy, routine lymph node sampling, the amount of resected thyroid tissue processed for histologic examination, and the absolute number of sections examined by the pathologist.

Adult↗

Suppressor cell activity in a proliferative disorder of T lymphocytes.

We report details of the immunological profile of a patient with the candidiasis endocrinopathy syndrome who has developed T-type chronic lymphocytic leukaemia. The patient is anergic to a panel of delayed hypersensitivity skin tests, and has poor in vitro mitogenic responses, but B cell function in vivo is not impaired. Subsequent functional studies have revealed that cells from the patient have a significant suppressive effect in coculture (P less than 0.05) on the responses of healthy donor lymphocytes (NR) to the mitogen phytohaemagglutinin (PHA). A degree of selectivity for the suppressive effect is suggested by the lack of similar effects on coculture responses to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Mitomycin C treatment of the patient's cells reduced their suppressive activity but significant suppression was still observed in the majority of PHA cocultures. The suppressor activity required the presence of the patient's cells in cocultures, as no suppression was observed when the patient's serum or cell culture supernatant were included instead of the patient's cells in NR cultures.

Adult↗

Anatagonism of the inhibitory effects of adenosine 5'-triphosphate on the isolated taenia of the guinea-pig caecum: structure-activity relationships within a series of isatogen derivatives.

1 A series of eight isatogen derivatives was studied on isolated tissues taken from guinea-pigs. The ability of the compounds to relax the taenia, to inhibit adenosine 5'-diphosphate (ADP)-stimulated respiration in mitochondria and to antagonize the inhibitory effects of adenosine 5'-triphosphate (ATP) on smooth muscle was measured. 2 All the derivatives inhibited ADP-stimulated respiration in mitochondria and relaxed the smooth muscle. These two effects were found to be significantly correlated. 3 Only half the compounds blocked the inhibitory effects of ATP, and all of these had a chemically reactive group (nitro, methoxy or pyridyl) in the 2'2-position. 2-2'-Pyridylisatogen was the most effective blocking agent. 4 The blockade of the inhibitory effects of ATP is not related to the other actions of the derivatives.

Adenosine Diphosphate↗