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Biomedical subjects

W Baker

Publications and source records attributed to W Baker.

At least 19 recordsLinked to original sources
PubMed1998

Tuberculosis: a search for novel therapy starting with natural products.

The reemergence of tuberculosis and closely related diseases as significant public health problems is briefly reviewed with particular emphasis on the exacerbating role of AIDS and multiple drug resistance. Screening methods available for discovering new chemical entities active against resistant strains are discussed and their use in screening extracts and compounds for activity is illustrated with a number of newly discovered structures being presented. In particular, the properties of the potent and structurally novel indoloquinazolinone alkaloid, tryptanthrin, is described. Many analogs of this lead structure were synthesized by combinatorial and multiple parallel synthetic techniques and evaluated in vitro and in vivo for their potential in the chemotherapy of human infections.

Animals↗
PubMed1998

Antitubercular natural products: berberine from the roots of commercial Hydrastis canadensis powder. Isolation of inactive 8-oxotetrahydrothalifendine, canadine, beta-hydrastine, and two new quinic acid esters, hycandinic acid esters-1 and -2.

Berberine (4) is responsible for the activity of an extract of a commercial root sample of Hydrastis canadensis against multiply drug resistant Mycobacterium tuberculosis. Two new quinic acid feruloyl esters, compounds 2 and 3, have been isolated from the same source along with canadine (1c), 8-oxotetrahydrothalifendine (1), and beta-hydrastine (5). These were found to be inactive. The structures of the new compounds were elucidated from spectral (1H, 13C, HMQC, HMBC, and H-H COSY) and chemical evidences.

Alkaloids↗
PubMed1997

Rapid screening of natural products for antimycobacterial activity by using luciferase-expressing strains of Mycobacterium bovis BCG and Mycobacterium intracellulare.

The object of this study was to investigate the ability of a rapid luciferase assay to detect antimycobacterial activity in plant extracts. Recombinant strains of Mycobacterium bovis BCG (rBCG) and Mycobacterium intracellulare expressing firefly luciferase were used as the test organisms. Assays were conducted in a 96-well minitube format under biosafety level 2 conditions. Control and test wells were sampled immediately after inoculation and after 3 (recombinant M. intracellulare) and 5 (rBCG) days of incubation to measure luminescence with a microplate luminometer, and the relative change in luminescence was calculated as a percentage of control values. As an alternative test method, Alamar blue was added after 12 days of incubation, and changes in color were read visually. A total of 480 extracts were tested. Sixteen extracts were active against rBCG, and of those, seven were also active against recombinant M. intracellulare. With activity defined as a relative change in luminescence of < or = 1% (i.e., > or = 99% inhibition) and a persistence of blue color after addition of Alamar blue, there was 99.0% agreement between the two methods. Our results suggest that the luciferase assay is rapid and accurate and has the potential to greatly accelerate the evaluation of antimycobacterial activity in plant extracts in vitro. With this method, it is possible to screen a large number of samples in a short period of time.

Anti-Bacterial Agents↗
PubMed1996

Immunogenicity and efficacy against lethal aerosol staphylococcal enterotoxin B challenge in monkeys by intramuscular and respiratory delivery of proteosome-toxoid vaccines.

Staphylococcal enterotoxin B (SEB), a primary cause of food poisoning, is also a superantigen that can cause toxic shock after traumatic or surgical staphylococcal wound [correction of would] infections or viral influenza-associated staphylococcal superinfections or when aerosolized for use as a potential biologic warfare threat agent. Intranasal or intramuscular (i.m.) immunization with formalinized SEB toxoid formulated with meningococcal outer membrane protein proteosomes has previously been shown to be immunogenic and protective against lethal respiratory or parenteral SEB challenge in murine models of SEB intoxication. Here, it is demonstrated that immunization of nonhuman primates with the proteosome-SEB toxoid vaccine is safe, immunogenic, and protective against lethal aerosol challenge with 15 50% lethal doses of SEB. Monkeys (10 per group) were primed i.m. and given booster injections by either the i.m. or intratracheal route without adverse side effects. Anamnestic anti-SEB serum immunoglobulin G (IgG) responses were elicited in all monkeys, but strong IgA responses in sera and bronchial secretions were elicited both pre- and post-SEB challenge only in monkeys given booster injections intratracheally. The proteosome-SEB toxoid vaccine was efficacious by both routes in protecting 100% of monkeys against severe symptomatology and death from aerosolized-SEB intoxication. These data confirm the safety, immunogenicity, and efficacy in monkeys of parenteral and respiratory vaccination with the proteosome-SEB toxoid, thereby supporting clinical trials of this vaccine in humans. The safety and enhancement of both bronchial and systemic IgA and IgG responses by the proteosome vaccine delivered by a respiratory route are also encouraging for the development of mucosally delivered proteosome vaccines to protect against SEB and other toxic or infectious respiratory pathogens.

Aerosols↗
PubMed1995

Medical disorders of adults with mental retardation: a population study.

This study was conducted to determine the frequency of medical disorders in people with mental retardation. The prevalence of mental retardation among adults, ages 20 to 50 years, living in Northern Sydney, was determined, and 202 persons were randomly selected for medical examination. Compared to the local population, the study group had significantly increased cardiovascular risk factors, rate of medical consultation, rate of hospitalization, and mortality. The research sample had an average 5.4 medical disorders per person, half of which had not been detected previously. We concluded that the provision of health care to adults with mental retardation needs to be improved.

Adult↗
PubMed1992

A fast track to IAIMS: the Vanderbilt University strategy.

In July 1991, Vanderbilt University Medical Center (VUMC) initiated a fast track approach to the implementation of an Integrated Academic Information Management System (IAIMS). The fast track approach has four elements: 1) an integrated organizational structure combining various operational information management units and the academic informatics program into a single entity to enhance efficiency; 2) technology transfer and network access to remote resources in preference to de novo development; 3) parallel IAIMS planning and infrastructure construction; 4) restriction of the scope of the initial IAIMS to permit a manageable implementation project. The fast track approach is intended to provide a truly functional IAIMS within a time period (7 years) associated with other major construction projects such as the building of a replacement hospital.

Integrated Advanced Information Management Systems↗
PubMed1990

Cerebral oxygen consumption during asphyxia in fetal sheep.

Cerebral blood flow and cerebral arteriovenous oxygen content difference were measured in 17 fetal sheep, and cerebral oxygen uptake was calculated. The measurements were made under control conditions and after profound fetal asphyxia induced of uterine blood flow for up to 90 min. In 14 of the fetal sheep, sequential measurements were made to examine hemodynamic changes and cerebral oxygen consumption at comparable intervals up to 36 min of asphyxia. These fetuses initially had elevated blood pressure and lowered heart rate became hypoxemic, hypercarbic, and acidotic. There was an initial decrease in cerebral oxygen consumption. Sequential measurements, however, showed a relative stability in this decreased oxygenation during 4 to 36 min of asphyxia despite a progressive metabolic acidosis. The cerebral fractional oxygen extraction remained unchanged despite a mean pH of 6.98 at 36 min. The calculated cerebral oxygen uptake during asphyxia in all 17 sheep was grouped according to whether the ascending aortic oxygen content was greater or less than 1.0 mmol/l. In the first group with mean ascending aortic oxygen content of 1.3 mmol/l, blood flow to the brain was increased and cerebral oxygen consumption was 85% of control. In the second group with mean arterial blood oxygen content of 0.8 mmol/l, there was a narrowing of the arteriovenous oxygen content difference, but no further increase in cerebral blood flow. Cerebral oxygen consumption was only 48% of control in this more asphyxiated group. We conclude that the degree of hypoxemia in the second group represents a point where physiologic mechanisms cannot compensate, and may be associated with neuronal damage.

Adrenal Glands↗
PubMed1984

Decreased sensitivity of early imaging with In-111 oxine-labeled leukocytes in detection of occult infection: concise communication.

Imaging with leukocytes labeled with indium-111 oxine is a sensitive technique for detecting sites of occult infection. Traditionally, imaging is performed 24 hr after injection. We undertook a prospective study of 35 patients (40 studies) with possible occult infection to see whether a 24-hr delay in imaging is really necessary. Patients were imaged at 1-4 hr and again at 24 hr after injection. The early images had a sensitivity of only 33%, compared with 95% for the 24-hr images. Of the seven studies that were positive on both early and delayed images, 71% had more intense uptake at 24 hr. There were no false-positive early images. We conclude that imaging 1-4 hr after injection with In-111 oxine-labeled leukocytes has a low sensitivity for detecting occult infection. However, a positive early image is specific for a site of infection.

Adult↗
PubMed1981

Congenital coronary aneurysms nine years following saphenous vein bypass graft surgery.

A 34-year-old woman with two congenital coronary aneurysms received a saphenous vein bypass graft (SVBG) as treatment for a thrombosed right coronary artery aneurysm 9 years ago. The angiographic and surgical findings were reported at that time [1]. In 1979, she received a sequential SVBG to the left anterior descending and first diagonal coronary arteries following recurrence of angina and progressive occlusion of the left coronary artery aneurysm. She is believed to have the longest angiographically documented course following operation, and her case history is reported to aid in establishing the natural history of this unusual condition and its surgical management.

Adult↗
PubMed1981

Laryngeal paralysis in Arabian foals associated with oral haloxon administration.

Bilateral laryngeal paralysis is described in 5 Arabian and part-Arabian foals aged between 23 and 35 days. Tracheotomies resulted in complete relief of dyspnoea. Two cases showed recovery of abductor function of the right arytenoid cartilage after 3 weeks and one of these cases later recovered left abductor function. Four of the foals were autopsied at various times from one week to 6 months after the onset of respiratory obstruction. Histology of the recurrent laryngeal nerves showed active Wallerian degeneration and loss of nerve fibres in many fascicles in cases affected for one to 2 weeks. In the longer standing cases there was a severe deficiency of myelinated fibres. Histology of the dorsal and lateral cricoarytenoid muscles showed no abnormalities in the cases affected from one to 5 weeks. However, in the foal affected for 6 months there was variation in fibre diameter in the left dorsal cricoarytenoid muscle; in sections stained for myosin ATPase there was evidence of muscle fibre type grouping in both left and right dorsal cricoarytenoid muscles. It is postulated that the most likely cause of the condition was oral haloxon administration which was given to the foals at a dose rate of 1 to 2 g at fortnightly intervals, beginning at 2 days of age.

Animals↗
PubMed1980

Local leukocyte mobilization in irradiated or cyclophosphamide-treated rats.

Sprague-Dawley rats made neutropenic by 60Co irradiation or cyclophosphamide treatment retained a limited capacity for mounting a local leukocyte mobilization (LLM) response. Rats irradiated with 700 rad 60Co lacked an LLM. Rats treated with 100 mg/kg cyclophosphamide showed no LLM following an initial low response when assayed originally.

Agranulocytosis↗