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Biomedical subjects

L Wolfe

Publications and source records attributed to L Wolfe.

At least 19 recordsLinked to original sources
PubMed1992

Purification and characterization of a cytosolic insulin-stimulated serine kinase from rat liver.

A cytosolic insulin-sensitive serine kinase has been purified to apparent homogeneity in parallel from livers of control or acutely insulin-treated rats. The kinase is labile and requires rapid purification for stability. The kinase migrates as a band of apparent Mr = 90,000 on denaturing gels and elutes as a monomer on Superose 12 gel filtration. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis and renaturation, the 90-kDa band presumed to be the kinase shows kinase activity toward myelin basic protein in situ. Substrates of the kinase include Leu-Arg-Arg-Ala-Ser-Leu-Gly (Kemptide), ribosomal protein S6, S6 peptide, a proline-rich peptide substrate, microtubule-associated protein 2, and myelin basic protein. The kinase also phosphorylates histones H1 and H2B, but does not autophosphorylate to a significant stoichiometry. The activity of the kinase is inhibited by fluoride, glycerophosphate, p-nitrophenyl phosphate, p-nitrophenol, heparin, quercetin, poly-L-lysine, and potassium phosphate, but is unaffected by calcium, cAMP, spermine, protein kinase inhibitor peptide, phorbol myristate acetate, calcium plus phosphatidylserine, or vanadate. The kinase will utilize magnesium (10 mM) as well as manganese (1 mM) as a cofactor for maximal phosphotransferase activity. The kinase is not detected by immunoblotting with antibodies directed against protein kinase C or type II S6 kinase. Taken together, these properties distinguish this kinase from other insulin-sensitive kinases that have been described previously. The purified kinase from livers of insulin-treated rats shows a 5-20-fold higher specific activity compared to enzyme prepared from control rats, suggesting a covalent modification as the mechanism of activation. Incubation of purified, insulin-stimulated kinase with purified phosphatase 2A leads to deactivation of the kinase activity, and the phosphatase inhibitor nitrophenyl phosphate blocks this deactivation. The insulin-activated kinase fails to immunoblot with anti-tyrosine phosphate antibodies. Taken together, these results indicate that insulin activates this novel cytosolic protein kinase by a mechanism that causes its phosphorylation on serine or threonine residues.

Amino Acid Sequence↗
PubMed1992

Gastric bypass for treating severe obesity.

Gastric bypass (RY-GBP) has a very small gastric pouch with a 1-cm diameter Roux-Y gastrojejunostomy. RY-GBP is associated with early satiety and an aversion to sweets secondary to dumping syndrome symptoms and has a significantly better weight loss than various gastroplasty procedures, including the vertical banded gastroplasty. However, it may be associated with vitamin B-12 deficiency and iron deficiency anemia in menstruating females, preventable with prophylactic oral iron and vitamin B-12. With an 80% 5 y follow-up, RY-GBP patients lose two-thirds of their excess weight within 2 y, 60% at 5 y, and greater than 50% at 9 y. The RY-GBP can be beaten by nibbling "junk foods" (potato or corn chips). Conversion to a malabsorptive procedure may cause severe malnutrition and fat-soluble vitamin deficiencies and should be used only for "superobese" patients who fail a standard RY-GBP and have severe comorbidity. RY-GBP is the most effective procedure for morbid obesity, especially in patients addicted to "sweets."

Gastric Bypass↗
PubMed1992

Long-term effects of gastric surgery for treating respiratory insufficiency of obesity.

The Pickwickian syndrome can be divided into two primary breathing disorders, which can affect patients alone or in combination: sleep apnea syndrome (SAS) and obesity hypoventilation syndrome (OHS). Between 1980 and 1990, 126 patients with respiratory insufficiency underwent gastric surgery for morbid obesity, 12.5% of the entire series. These patients weighed more (164 +/- 36 vs 135 +/- 25 kg, P less than 0.0001) and were more often men (62% vs 14%, P less than 0.001) than those without pulmonary dysfunction. Sixteen had OHS alone, 65 had SAS alone, and 45 had both. Of those with OHS, 38 have been followed for 5.8 +/- 2.4 y since surgery and 29 are currently asymptomatic. In the 12 patients in whom arterial blood gases were available greater than 5 y since surgery, the PaO2 increased from 54 +/- 10 to 68 +/- 20 mm Hg (P less than 0.0001) and PaCO2 fell from 53 +/- 9 to 47 +/- 11 mm Hg (P = 0.05). Of the 110 patients with SAS, 57 were available for follow-up an average of 4.5 +/- 2.3 y since surgery and 38 were completely asymptomatic, 15 had mild SAS, and 4 had both SAS and OHS. In 40 patients with pre- and post-weight reduction sleep polysomnograms, the sleep apnea index fell from 64 +/- 39 to 26 +/- 26 (P less than 0.0001). Although respiratory insufficiency of obesity patients had a higher operative mortality than did patients without pulmonary dysfunction (2.4% vs 0.2% after gastric bypass), weight loss was associated with significant improvements in sleep apnea, arterial blood gases, pulmonary hypertension, left ventricular dysfunction, lung volumes, and polycythemia.

Adult↗
PubMed1992

Relaxation of pig coronary arteries by new and potent cGMP analogs that selectively activate type I alpha, compared with type I beta, cGMP-dependent protein kinase.

Smooth muscle preparations of human aorta or pig coronary arteries contain nearly equal amounts of cGMP-dependent protein kinase isozymes (cGMP kinase I alpha and I beta). In order to understand the roles of these isozymes in relaxing vascular smooth muscle, several new cGMP analogs were synthesized and tested for potencies in activating each enzyme and in relaxing pig coronary arteries. Analogs modified with a derivatized phenylthio group at the 8-position were as much as 72-fold more potent in activating purified cGMP kinase I alpha than cGMP kinase I beta. Electron-donating substituents, such as hydroxy, amino, and methoxy, on the phenyl ring enhanced the potencies of these analogs in activating cGMP kinase I alpha. The most potent of these cGMP analogs [8-(4-hydroxyphenylthio)-cGMP] was 17 times more potent (EC50 = 1.1 microM) as a muscle relaxant than the most efficacious analog tested previously. Among derivatives with an 8-halo group, 8-iodo-cGMP was the most potent compound (Ka = 9 nM for I alpha and 122 nM for I beta) for both I alpha and I beta. Analogs modified at the 1,N2-position or at both the 1,N2-and 8-positions of cGMP were highly potent for activating both isozymes. Within this group, 8-I-beta-phenyl-1,N2-etheno-cGMP had Ka values of 22 nM and 17 nM for cGMP kinase I alpha and I beta, respectively, whereas the Ka values of cGMP were 110 nM and 250 nM for the two isozymes. 8-I-beta-phenyl-1,N2-etheno-cGMP was the most potent muscle relaxant tested, with EC50 of 0.4 microM. For all cGMP analogs tested, there was a positive correlation between potency for activation of cGMP kinase I alpha and that for relaxation of pig coronary arteries. Assuming that the kinase assay conditions yielded a cyclic nucleotide specificity similar to that which would exist in intact cells, it was concluded that the cGMP kinase I alpha isozyme mediates the relaxation of pig coronary artery smooth muscle caused by cGMP elevation. However, an additional role for cGMP kinase I beta in the relaxation process could not be ruled out.

Animals↗
PubMed1992

Musculoskeletal tumors in childhood.

As treatment strategies improve, the ability to cure children with musculoskeletal tumors is growing. The stage of a given malignancy, representing the degree of spread of the tumor to its local surroundings or distant sites, is the best predictor of long-term survival. Unfortunately, the insidious nature of the presentation of these tumors leads to their late recognition in advanced stages. This review will present scenarios suggesting the need for consideration of malignancy in the differential diagnosis of clinical problems related to the musculoskeletal system. Pitfalls in diagnosis and therapeutic approaches will also be discussed.

Bone Neoplasms↗
PubMed1992

Stomal complications of gastric bypass: incidence and outcome of therapy.

Gastric bypass is an effective treatment for morbid obesity. However, it is sometimes complicated by stenosis or ulceration of the gastrojejunal anastomosis. Stomal ulceration and stenosis developed in, respectively, 12.5% and 12% of 191 patients who underwent gastric bypass. Only 3% had both complications simultaneously. The risk of developing either complication was highest in the first 2 months after surgery. Stomal stenosis responded to endoscopic dilation in all instances, and appears to be a safe and effective method of treating this problem following gastric bypass. Stomal ulceration healed with an H2 blocker and sucralfate administration in all but one patient. Postoperative weight loss was similar in patients with or without stomal stenosis or ulceration. We conclude that, although stomal complications occur in about 20% of all patients undergoing gastric bypass, they can almost always be managed by conservative therapy.

Catheterization↗
PubMed1991

Dynamic pressure analysis of the diabetic charcot foot.

Charcot foot is a form of neuropathic osteoarthropathy, occurring in one or more joints of the foot and ankle. It is a destructive process that alters the weightbearing areas of the foot and, in many cases, results in a rocker-bottom deformity. The authors present quantitative results of dynamic pressure analysis of Charcot foot with the EMED SF pressure analysis system and propose ways in which this information may be used in the evaluation and treatment of this deformity.

Adult↗
PubMed1978

Age and sexual behavior of Japanese macaques (Macaca fuscata).

The sexual behavior of the Arashiyama West troop, a natural semi-free-ranging troop of Japanese macaques, was studied during the 1973-1974 and 1974-1975 breeding seasons. The troop was transported intact from Japan to its current location in South Texas. There they have been free to move about in a 42.2-hectare electric fence enclosure. This report describes the relationships among age, aging, and sexual behavior. Males beginning at the age of 2.5 years were observed to series-mount estrous females in the double foot clasp mount position. Mounting in series in the double foot position is the normal pattern for Japanese macaque males. The ejaculation of semen with concomitant body movements indicative of orgasm begins at age 4.5 years at the earliest and continues until death. Males 4.5 and 5.5 years of age, sexually mature in the physiological sense, were not consistently sexually mature in the behavioral sense. The oldest male displayed traits that appear analogous to traits observed in aging human males. Females begin to experience estrus at 3.5 years of age. However, like pubescent males, pubescent females display behavioral patterns of sexual immaturity. The oldest female of the troop has remained sexually active. The attainment of sexual maturity by adulthood can be viewed as a learned process leading to efficiency and prowess, followed in old age by sexual involution.

Aging↗
PubMed1976

Epstein-Barr virus: experimental infection of Callithrix jacchus marmosets.

Eight common marmoset monkeys (Callithrix jacchus) were inoculated with about 10(4) transforming units of B95-8 virus; seven of the marmosets died 50-111 days post inoculation and all seven showed microscopic and/or macroscopic lesions compatible with a diagnosis of lymphoproliferative disease. Low levels of anti-VCA antibodies were detected in plasma from six marmosets. Attempts failed to establish continuous EBV-carrying lymphoblastoid cell cultures by cultivation in vitro of circulating lymphocytes or minced lymphoid tissues obtained at necropsy.

Animals↗
PubMed1976

Experimental infection of squirrel and marmoset monkeys with attenuated Herpesvirus saimiri.

Herpesvirus saimiri (HVS) was propagated in vero cells for 3 passages at 39 degrees and cloned 3 times at 34 degrees. This virus was inoculated into cotton-topped marmoset and squirrel monkeys; all inoculated monkeys became infected as HVS was reisolated after their circulating lymphocytes were cultured with vero cells and measurable levels of antiviral antibodies developed that were measured by immunofluorescence and/or neutralization tests. None of the inoculated monkeys developed any signs of overt disease and all inoculated monkeys have survived 9 to 14 months postinoculation. The attenuated virus appears to be genetically stable as virus isolated from an infected marmoset was passed 3 times in vitro and then inoculated into other marmosets, which became infected and remained clinically well. Marmosets latently infected with attenuated HVS were not protected when challenged with a large dose (770 plaque-forming units) of oncogenic HVS, although these marmosets survived about 3 times longer than did inoculated control marmosets.

Animals↗
PubMed1975

Immunological control of virus-induced tumors in primates.

Cells infected by oncogenic viruses may transform, may develop a latent carrier state, or may be destroyed but understanding of the control of the results of infection is incomplete. Even if cells transform, ultimate development of a tumor may be immunologically controlled. For example, cells of some marmoset species transform after infection with RNA tumor viruses, and animals react to the transformed cells with cell-mediated and humoral immune responses. Both virus specific and cross-reacting cell membrane antigens have been demonstrated. Immune deficiency accelerates tumor growth or causes recurrence of a regressing tumor. In contrast certain simian herpesvirus (Herpesvirus saimiri, HVS and Herpesvirus ateles, HVA), which cause no or minor disease in their natural hosts, induce lymphomas or lymphoblastic leukemias in other primate species. The immune response of the natural host species to HVS is greater than that of animals developing malignancies after experimental infection. HVS and HVA share many properties with Epstein-Barr virus (EBV) of man, including antigens appearing early and late during infection and their related antibody responses but no evidence exists that they induce malignancies in their natural hosts. However, if induction is as infrequent as that with EBV and Burkitt's lymphoma (BL), we have not observed sufficient numbers of squirrel or spider monkeys to have seen a BL-like tumor. Interference with the immune systems of animals carrying HVS or HVA may induce tumor development, and clarify our understanding of the relationships between EBV and BL.

Animals↗
PubMed1975

The mythology of various hepatitis A virus isolates.

Several types of viral hepatitis may exist. Hepatitis A (MS-1 type) can be transmitted to marmosets and chimpanzees. Virus-like particles, which may be parvo- or enteroviruses and which have been demonstrated in feces of this type of hepatitis, do not share cross-reacting antigens with hepatitis B but do cross-react with fecal hepatitis A antigen. Hepatitis A (GB type), which also does not cross-react with hepatitis B, is not antigenically identical with MS-1; it can be transmitted to marmosets and it may be similar to non-type A/non-type B post-transfusion hepatitis. Hepatitits B does not cross-react either with HA particles, the faecal hepatitis type A antigen or with the MS-1 or GB strains; it can be transmitted to chimpanzees and rhesus monkeys but not to marmosets.

Animals↗
PubMed1975

Transformation in vitro with herpesvirus ateles.

Continuous lymphoblastoid cell cultures were established after transformation invitro with HVA of marmoset splenic or circulating lymphocytes. Transformation was achieved by co-cultivating lymphocytes with lethally X-irradiated, HVA-carrying cells (derived originally from tumour cells of a marmoset experimentally infected with HVA) or by infecting marmoset lymphocytes with cell-free virus. Tenty-eight continous cultures from 39 that underwent co-cultivation and two of four lymphocyte preparations infected with virus became transformed. Cultivation periods before transformation were in the range 17-32 days (co-cultivation) or 51-53 days (cell-free virus). HVA genome expression in transfromed cultures was demonstrated by:(1) recovery of small amounts of HVA from culture fluids; (2) ability of lymphoblasts to induce infectious centres after co-cultivation with permissive cells; and (3) observation of antigen-positive cells after staining with monospecific antiserum. Most cultures were composed of T lymphocytes: cells of 16 of 24 cultures formed rosettes with sheep erythrocytes and none of 30 possessed membrane Ig.

Animals↗