Psychological characteristics of elite wheelchair athletes: the iceberg profile.
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Adult↗
Biomedical subjects
W Harris
Publications and source records attributed to W Harris.
Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation.
Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.
Administration, Oral↗
Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction.
The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.
Alkaloids↗
The contribution of the nonporous distal stem to the stability of proximally porous-coated canine femoral components.
The contribution of the distal nonporous-coated stem to the stability of the uncemented femoral components, which were porous coated only proximally, was investigated under two conditions: (1) immediately after insertion and (2) at 6 months, 1 year, and 2 years after surgery in a canine model. The relative motion of the femoral components at the bone porous-coating interface under loads simulating the canine midstance was measured at these time periods using displacement transducers. The measurements were repeated after severing the connection between the porous-coated proximal body and the nonporous-coated distal stem through a small hole in the anterior cortex. The results showed that while the distal nonporous-coated stem enhanced the immediate stability of the proximally porous-coated uncemented femoral components, it contributed little to the long-term stability of the femoral components after bony ingrowth had occurred in vivo. The mean relative motion between the body of the prosthesis and the cortical bone increased from 12 microns (+/- 7 microns) to 31 microns (+/- 34 microns) in the posterior transverse direction when the stem was immediately severed after the surgery. However, at 6 months, 1 year, and 2 years after surgery, extensive bone ingrowth had occurred into the proximal porous-coated regions of the body and provided excellent stability to the femoral components. With bone ingrowth, the mean relative motion was less than 5 microns at any site. Under these conditions, severing the stem did not increase the relative motion of the prostheses significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Alloys↗
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↗
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↗
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↗
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↗
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↗
Buspirone suppression of neuroleptic-induced akathisia: multiple case reports.
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Adult↗
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↗
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↗
Single-dose and multiple-dose pharmacokinetics of etintidine in healthy volunteers.
The present study was designed to determine the single- and multiple-dose pharmacokinetic profiles of the H2 receptor antagonist etintidine in healthy volunteers. Etintidine was rapidly absorbed and eliminated after the oral administration of 300 mg base equivalent of etintidine HCl in a capsule formulation to 11 healthy subjects. Comparison of the pharmacokinetics after a single dose and during steady state showed no significant differences (p greater than 0.05) in the mean values of Cmax, tmax, oral clearance, elimination rate constant, and renal clearance, indicating no significant accumulation of etintidine and no apparent time-dependent changes in the pharmacokinetics of etintidine during multiple dose administration.
Absorption↗
Reproducibility of individual serum cholesterol response to diet.
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Cholesterol↗
Suppression of HIV p24 antigen and induction of HIV anti-p24 antibody by alpha interferon in patients with chronic hepatitis B.
Five HIV p24 antigen (p24Ag)-positive patients received alpha interferon during trials of therapy for hepatitis B. Four of these showed marked falls in p24Ag during treatment. One of the two patients who became p24Ag-negative [corrected] developed anti-p24 antibodies (anti-p24). Five out of nine p24Ag-negative HIV-antibody-positive patients showed a rise in anti-p24 titres during interferon therapy, whereas only two out of six untreated controls showed a similar rise. This study provides evidence that alpha interferon has anti-HIV activity in vivo.
Adult↗
Treatment of endogenous uveitis with cyclosporine A.
Thirty patients suffering from severe sight-threatening bilateral chronic endogenous uveitis were treated with initial dosages of 10 mg/kg/d of CsA. After 1 month of therapy, all patients but one demonstrated a rapid decrease of the intraocular inflammatory processes along with an arrest of the deterioration of vision. After 1 year (or more) of treatment, most patients still show the same visual acuity achieved after 1 month. During the 3-year span of this study, attempts at tapering off the CsA dosage to less than 5 mg/kg/d induced a temporary flare-up in 20 of the 24 patients followed without interruption for more than 6 months. Nonetheless, control of the intraocular inflammation was finally achieved by 5 mg CsA/kg/d or less in 14 of the 25 patients. In six of these 14 patients the CsA dosage was further tapered to total discontinuation. Two of the six patients showed a rapid reactivation of the intraocular inflammatory processes with a profound decrease in vision within 1 and 3 weeks, respectively. In four patients, control of the intraocular inflammation and preservation of good visual acuity have been observed for a period of up to 18 months.
Behcet Syndrome↗
Evaluation of conventional therapy versus cyclosporine A in Behçet's syndrome.
When ocular structures are affected in Behçet's syndrome, a rapid loss of vision has been the rule regardless of the type of treatment--corticosteroids, Leukeran, Imuran, colchicine. The objectives of the present study were to compare, in a masked manner, conventional treatment (corticosteroids/Leukeran) to treatment with CsA. Forty patients suffering from Behçet's syndrome with active ocular inflammatory reactions were included in the study. These were randomly assigned to conventional or CsA regimens and were regularly examined by a multidisciplinary group of physicians. The unmasked internist modulated the treatment and recorded systemic manifestations. The masked ophthalmologists recorded the ocular findings without knowledge of the assigned type of treatment. An analysis of the results 3 years after initiation of the study shows that CsA is more effective than conventional therapy in decreasing the active ocular inflammatory processes and arresting the deterioration of visual acuity. Regarding the extraocular symptoms, however, conventional therapy is superior to CsA, especially for the control of skin lesions and arthritis. Side effects were recorded in a much higher incidence among patients receiving CsA. However, tight and constant control of the CsA dosage as performed in this study has, so far, prevented clinical and biochemical nephrotoxic manifestations in patients assigned to this treatment.
Adrenal Cortex Hormones↗
The effects of chiropractic adjustments on distal skin temperature.
Stimulation of the sympathetic nervous system will cause a reduction in the skin blood flow which can be detected by measuring the skin surface temperature. The purpose of this study was to see whether chiropractic adjustments could affect the activity of the sympathetic nervous system as reflected by changes in distal (fingertip) skin temperature. Skin temperature on 196 subjects was measured before and within 10 sec after a spinal adjustment. The difference between the pre- and post-temperatures was determined. The average fingertip temperature did not change when the spine was considered as an entire unit. However, when sympathetic and nonsympathetic regions were analyzed separately, we found significant differences in temperature response. The average temperature rose from 85.84 +/- 6.04 degrees F to 86.26 +/- 6.25 degrees F when C1-C7 and/or L4-L5 were adjusted (p less than 0.001). When the area between T1-L3 was adjusted, however, the average temperature fell from 84.97 +/- 6.11 degrees F to 84.72 +/- 6.19 degrees F (p less than 0.001). These results illustrate that the blood flow through the fingertips can be affected by specific adjustments to the spine, and, further, that the response varies, depending on the location of the adjustment. Thus, adjustments to the spine can, via stimulation of the nervous system, affect the physiology of tissues distant from the spine.
Chiropractic↗