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Biomedical subjects

W Harris

Publications and source records attributed to W Harris.

13 recordsLinked to original sources
PubMed1992

Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity.

A hypothetical mode of inhibition of protein kinase C (PKC) by the natural product staurosporine has been used as a basis for the design of substituted bisindolylmaleimides with improved potency over the parent compound. Structure-activity relationships were consistent with the interaction of a cationic group in the inhibitor with a carboxylate group in the enzyme, and the most potent compound had a Ki of 3 nM. The inhibitors were competitive with ATP but inhibited cAMP-dependent protein kinase (PKA) only at much higher concentrations despite the extensive sequence homology between the ATP-binding regions of PKA and PKC. Three compounds were evaluated further and found to inhibit a human allogeneic mixed lymphocyte reaction pointing to the potential utility of PKC inhibitors in immunosuppressive therapy. One of these compounds was orally absorbed in the rat and represents an attractive lead in the development of PKC inhibitors as drugs.

Animals↗
PubMed1992

Unrecognized femoral fractures during cementless total hip arthroplasty in the dog and their effect on bone ingrowth.

Uncemented straight-stemmed proximally porous-coated femoral components were press fitted into the femoral canals of seven dogs using a rasp 0.5 mm smaller than the components (press-fit group). In seven other dogs the components were fit precisely into the femoral canals using a rasp that was the same size as the components (control group). Using this technique, all of the dogs in the press-fit group developed longitudinal fractures in the femoral cortex, while none of the dogs in the control group developed fractures. None of the fractures were recognized at operation. Two of the dogs in the press-fit group displaced the fractures at 1 week and were sacrificed. The other five dogs were bearing weight on their limbs and completed the 3-week experimental period. Follow-up radiographs of these femurs showed marked periosteal new bone formation, but did not reveal any fractures. Serial sections of these femurs showed longitudinal healing fractures in the anterior cortex. The fractures had an adverse effect on the bone ingrowth into the porous surface of the press-fit group compared to the control group without fractures, and the porous surface adjacent to the fractures was ingrown with fibrous tissue. The amount of bone ingrowth expressed as a percentage of the porous coating area measured, on average, only 3.9% in the press-fit group at 3 weeks compared to 5.6% in the control group--a statistically significant difference at P < .025. This experience in the dog illustrates the inherent risk of driving a larger femoral component into a smaller cavity prepared in the femur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Xotch, the Xenopus homolog of Drosophila notch.

During the development of a vertebrate embryo, cell fate is determined by inductive signals passing between neighboring tissues. Such determinative interactions have been difficult to characterize fully without knowledge of the molecular mechanisms involved. Mutations of Drosophila and the nematode Caenorhabditis elegans have been isolated that define a family of related gene products involved in similar types of cellular inductions. One of these genes, the Notch gene from Drosophila, is involved with cell fate choices in the neurogenic region of the blastoderm, in the developing nervous system, and in the eye-antennal imaginal disc. Complementary DNA clones were isolated from Xenopus embryos with Notch DNA in order to investigate whether cell-cell interactions in vertebrate embryos also depend on Notch-like molecules. This approach identified a Xenopus molecule, Xotch, which is remarkably similar to Drosophila Notch in both structure and developmental expression.

Amino Acid Sequence↗
PubMed1990

Ultrastructure of the jejunal mucosa in human immunodeficiency virus infection.

The ultrastructural changes in the jejunal mucosa of 11 male patients, three with clinical AIDS, five with AIDS related complex-progressive generalized lymphadenopathy (ARC-PGL), and three who were only HIV antibody positive, were studied. In the enterocytes, major abnormalities were proliferation of smooth endoplasmic reticulum mitochondrial changes, vacuolization of cells, and fat hold up. In the lamina propria, degeneration of enteric nerve axons and smooth muscle were seen. Microvasculature showed both endothelial cell degeneration and hyperplasia. The presence of tubuloreticular inclusions in endothelial cells paralleled the stage of the disease. Since none of the 11 patients had any opportunistic infection, these changes are likely to be the effect of HIV infection.

AIDS-Related Complex↗
PubMed1990

Where there's smoke...carbon monoxide exposures in smoking and smoke-free workplaces.

Comparisons of expired air carbon monoxide levels in non-smoking staff in six licensed clubs (a smoking workplace) were made with those of non-smoking staff of a large public hospital (a smoke-free workplace). There was a significant difference between clubs and hospital in levels of CO at end of work. The average concentration of club workers was 8.7 ppm (Hospital, 5.3 ppm). Approximately one third of these non-smokers in licensed clubs exceeded 10 ppm putting them in the 'light smoker' category according to the manufacturer of the monitoring equipment. Club workers increased their CO level during work time by four times the increase of Hospital staff. This study suggests that there are significant gains to be made in reduction of intake of harmful passive-smoking products by removing tobacco smoke from workplaces.

Australia↗
PubMed1989

Giant Brenner tumor. Case report.

A case is reported of an unusually large benign cystic Brenner tumor. Larger solid tumors have been reported, and, additionally, proliferating Brenner tumors are most often large and cystic. However, the tumor described in this presentation appears to be the largest entirely cystic Brenner tumor reported to date.

Adult↗
PubMed1989

ELISA HIV testing and viral culture in the screening of corneal tissue for transplant from medical examiner cases.

The spread of AIDS and its association with a retrovirus, commonly called T-lymphotropic virus type III (HIV) has produced great concern among those involved in transplantation about the possibility for transmission of this disease through tissue and organ transplant. Isolation of the virus from conjunctiva and tears further heightened this concern for corneal transplants. This review of medical examiner (ME) cases, a population in which high numbers of transplant corneas are retrieved, has revealed positive serologic tests for HIV in serum from 5 cases in 205 screens. These represent potential donors based on other standard medical criteria available at the time of collection. This tissue was also submitted for viral culture, and virus was recovered from the corneal tissue in McCarey-Kaufman (MK) media. These findings and case reviews are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1977

A nurse rehabilitator's impact on patients with myocardial infarction.

A nurse rehabilitator, supplementing routine physician/nursing coronary care unit (CCU) care, was found to be effective in increasing the return to work rate (p less than .05) and decreasing smoking (p less than .05) in a randomized trial of 102 patients with acute myocardial infarction (MI). These outcomes were thought to be due to the nurse rehabilitator's efforts in increasing patient knowledge of heart disease (p less than .01) and individual counseling.

Adult↗