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Biomedical subjects

M J White

Publications and source records attributed to M J White.

At least 37 records · Page 2Linked to original sources
PubMed1999

Adoptively transferable tolerance induced by CD45RB monoclonal antibody.

The phenomenon of rejection remains the most serious problem in transplantation. The ultimate goal in transplant immunology is to develop therapeutic strategies that lead to tolerance. It has been shown that two injections of a monoclonal antibody to CD45RB leads to indefinite acceptance of renal allografts in mice. Moreover, the CD45RB monoclonal antibody reverses acute rejection and still induces tolerance. The purpose of this study was to assess mechanisms that could underlie this therapeutic benefit. It was shown that splenic lymphocytes from tolerant animals augmented proliferation in allogeneic mixed lymphocyte reactions against donor alloantigens, and the serum of tolerant mice contained donor-specific antibodies, mainly of the IgG1 isotype, suggesting the presence of TH2 cytokines. Tolerance could not be broken by interleukin-2 infusion, but tolerance could be adoptively transferred by transfusion of tolerant mouse CD4+ splenic lymphocytes into naive allografted animals. These data suggest that an active immunoregulatory mechanism is partly responsible for the therapeutic effect. CD45RB-directed therapy may find clinical application in organ transplantation in human patients.

Adoptive Transfer↗
PubMed1997

A Bcl-2 antisense oligonucleotide increases alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) toxicity in cortical cultures.

Both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated neurotoxicity and the induction of death-regulatory genes have been implicated in the pathophysiology of delayed ischemic neuronal injury. To assess the role of the antiapoptotic gene Bcl-2 in the modulation of AMPA toxicity, we exposed neuron-enriched cultures from rat cerebral cortex to AMPA, in the absence or presence of an antisense oligodeoxynucleotide (ODN) directed against Bcl-2. AMPA produced concentration-dependent toxicity detected by a decrease in fluorescence of the redox indicator Alamar blue and by an increase in lactic acid dehydrogenase release. This effect was accompanied by the induction of Bcl-2 protein expression, with maximal induction at 100 microM AMPA. A phosphorothioate antisense ODN against Bcl-2 reduced the AMPA-stimulated induction of Bcl-2 protein levels, detected by western blotting, by about 70%. In the presence of the antisense ODN, but not sense or scrambled ODNs, the toxicity of 100 microM AMPA was increased by about 60%. These findings suggest that induction of Bcl-2 expression by AMPA may have a protective role to limit AMPA receptor-mediated neuronal damage and that modifying Bcl-2 expression could have therapeutic potential in ischemia.

Animals↗
PubMed1996

Assessment of neuronal viability with Alamar blue in cortical and granule cell cultures.

Alamar blue, a redox indicator of cell viability in nonneuronal systems, was used to assess neuronal viability in cultures prepared from embryonic rat cerebral cortex and neonatal rat cerebellum. Alamar blue fluorescence varied linearly with cell number and was decreased by treating cortical or cerebellar granule cell cultures with excitatory amino acids, exposing cortical cultures to hypoxia and glucose deprivation, or inducing apoptotic death in granule cell cultures by growth in medium containing a low concentration of K+. Alamar blue fluorescence may complement existing methods for measuring neuronal viability and cytotoxicity in culture and thereby contribute to the study of cellular mechanisms of neurologic disease.

Animals↗
PubMed1996

Treatment of experimental brain injury with moderate hypothermia and 21-aminosteroids.

Studies of experimental traumatic brain injury have found that histologic injury is significantly reduced and behavioral outcome improved in animals treated with moderate hypothermia (32-33 degrees C) or a 21-aminosteroid. Because these treatments are thought to work through different neurochemical mechanisms, their combined use might be expected to be more efficacious than either treatment alone. To test this hypothesis, we studied each treatment separately and in combination in a rodent model of controlled cortical contusion. Treatment with moderate hypothermia (32 degrees C for 4 h), a 21-aminosteroid (U-74389G, Upjohn, 10 mg/kg intravenously, repeated 3 h after the first dose), or both, was initiated 10, 25, or 40 min after injury. The brains were perfused 24 h after injury, and sagittal sections were stained for the 68-kDa "core" neurofilament subunit, a marker of axonal injury. The total number of positively stained axons in the ipsilateral internal capsule were counted under light microscopy. Compared with the control group (injury but no treatment), treatment with each therapy alone or combined, initiated 10 min after injury, caused significant reductions in the number of stained axons (21-aminosteroid alone-35% reduction; hypothermia alone-55% reduction; combination-48% reduction). The number of positively stained axons was significantly reduced in the aminosteroid and combination therapy groups at all three postinjury times (p = 0.01) and in the hypothermia groups treated at 10 or 25 min (p = 0.01) but not at 40 min after injury. We concluded that combination therapy with hypothermia and 21-aminosteroids was no more efficacious than either therapy alone, and that 21-aminosteroid therapy was more efficacious than hypothermia when treatment was initiated 40 min after injury.

Animals↗
PubMed1996

Perceptions of practicing CNSs about their future role.

With the evolution of the clinical nurse specialist (CNS) and nurse practitioner (NP) roles and with the changes in the healthcare delivery system, recent debate in advanced practice nursing has centered on blending or merging the roles to meet future healthcare needs. To determine the views of CNSs, the University of Texas at Houston Health Science Center School of Nursing conducted a survey of 80 nurses (all active graduate program preceptors) functioning in the CNS role in the Houston area. Respondents were asked whether they felt the role should be deleted or merged, their ideas for the future of the role, and how education could better prepare the CNS student. Forty-two questionnaires were returned (53% return). Twenty-nine (71%) respondents did not want the role deleted, seven (17%) favored deletion of the CNS role, five (12%) favored blending the CNS and NP roles, and one (0.02%) suggested the title of acute care nurse practitioner. Although the survey's results did not show overwhelming support for either deletion or merging of the CNS role, valuable information was gathered from the responses. The CNS community identified recommendations that will help shape our focus for practice and guide us in educational design in curriculum revision.

Attitude of Health Personnel↗
PubMed1996

Internal migration in China, 1950-1988.

This paper examines the long-term patterns of migration within China between 1950 and 1988. The analysis uses data from China's 1988 2/1,000 Fertility and Birth Control Survey, which asks respondents about their most recent interprovincial move. The results suggest that long-term migration patterns can be explained by political and economic changes in China. We argue that the approaches we introduce can offer significant insight into long-term migration patterns for countries where historical data on migration are unavailable or unreliable.

China↗
PubMed1995

The relationship between the pressor response to involuntary isometric exercise and the contractile protein profile of the active muscle in man.

The present investigation examined the relationship between the pressor response during electrically evoked isometric ankle plantar flexion and the contractile protein profile of the active muscle in seven young men [mean (SD) age, 26 (6) years] and five older men [70 (4) years]. Muscle biopsy samples were taken from lateral gastrocnemius (LG) and soleus (SOL) of each subject. These were analysed for isomyosin composition using non-denaturing pyrophosphate polyacrylamide gel electrophoresis. The degree of association was examined between the cardiovascular changes and the fast isomyosin content of LG and SOL individually and in combination (SOL/LG). In the total subject group there was no association between the heart rate response or the change in systolic blood pressure (BP) and the fast isomyosin composition. However, the change in diastolic BP was significantly associated with the fast isomyosin composition of SOL/LG (delta diastolicBP = 0.31 + 0.045% FM SOL/LG, r = 0.65, P = 0.029). These findings suggest that the magnitude of the peripheral reflex mediated pressor response to isometric exercise and the fast isomyosin content of the active muscle are related.

Adult↗
PubMed1995

Gastrocnemius muscle transposition to the femur: how high can you go?

The gastrocnemius muscle flap has gained wide acceptance as a reconstructive technique for management of wounds of the knee and proximal tibia. The use of the muscle as a pedicle flap to the distal and middle femur has not been well quantified, and the proximal rotation arc has been underestimated. We report the use of the island gastrocnemius pedicle flap to reach two femur defects 21 and 26 cm above the joint line, achieved by taking advantage of the favorable location of the vascular pedicle above the joint line and the individual length of the medial gastrocnemius muscle belly. Evaluation of standard arteriograms suggests the location of the medial sural artery pedicle is an average of 32 +/- 14.5 (SD) mm above the inferior border of the femur. All vessel origins were found above the joint line by radiograph. A common sural artery origin was noted in 32% of patients at a mean distance of 35 mm proximal to the joint line. Despite a wide range, 62% of sural artery origins were within 1 cm of an axis drawn through the widest point of the femoral condyles.

Adult↗
PubMed1995

Electrically evoked torque-velocity characteristics and isomyosin composition of the triceps surae in young and elderly men.

The electrically evoked isokinetic torque-velocity relationship of the triceps surae of eight elderly and four non-trained young men was examined in relation to the isomyosin composition of the soleus and the gastrocnemius muscles, determined under non-denaturing conditions using pyrophosphate gel electrophoresis. The angle specific torque-velocity properties of the triceps surae were measured using maximal percutaneous electrical stimulation at 50 Hz and a release technique. The elderly subjects generated significantly (P < 0.05) less absolute torque at all angular velocities when compared with the young subjects. When the isokinetic data were normalized to the isometric torque, the lower normalized torques generated by the elderly subjects were not statistically different from the young. The total fast isomyosin (FM) content of the soleus and gastrocnemius in the elderly subjects was 22 +/- 13 and 35+/- 18%, respectively. This compared with 29 +/- 8 (n.s) and 44 +/- 8% (n.s.) in the young subjects. When the gastrocnemius and soleus muscles were given an equal weighting and considered together to represent the whole triceps surae, the normalized torque at the fixed angular velocity of 5 rads s-1 was significantly associated with %FM (r = 0.90, P < 0.01), and the isomyosin bands %FM1 (r = 0.90, P < 0.01) and %FM2 (r = 0.93, P < 0.001) when only the elderly subjects were considered. No relationships were observed between contractile characteristics and contractile protein profile when only the young subjects were considered. This was despite the inclusion of a further two sprint and three endurance trained athletes to increase the range of contractile characteristics and differences in muscle composition.

Adult↗
PubMed1995

Diagnostic overshadowing and mental retardation: a meta-analysis.

Clinicians who minimize the significance of emotional disorders in persons with mental retardation may be displaying the diagnostic overshadowing judgmental bias. A meta-analysis of the existing literature on this bias was conducted to determine its reliability, the size of its effect, and its potential clinical significance. Results show the effect to be reliable across studies; the size of the effect was small to moderate. Interpretation of the clinical significance of these results is clouded by the absence of in vivo studies. Additional concerns include insufficient attention given to clinician and situational variables moderating the presence of diagnostic overshadowing.

Humans↗
PubMed1994

The value of liability in medical malpractice.

In this paper I estimate the strength of medical providers' incentive to avoid negligent medical care, taking account of the facts that many victims of medical malpractice do not file claims, many nonvictims do file claims, legal costs are high, and the legal system makes errors. Despite these problems, the negligence system creates a strong financial incentive for medical providers to avoid substandard care: The average cost of negligence is $135,000 per malpractice claim involving negligence and $3,500 per occurrence of negligent medical care. These substantial penalties suggest that if liability were abolished without adopting effective alternative sanctions for negligent medical care, the number and cost of medically caused injuries and deaths could rise sharply.

Consumer Advocacy↗
PubMed1994

Anti-B cell antibodies for the treatment of monoclonal Epstein-Barr virus-induced lymphoproliferative syndrome after multivisceral transplantation.

Epstein-Barr virus-induced lymphoproliferative syndrome (EBV-LPS) is associated with OKT3 therapy in transplant patients. Response to chemotherapy or radiation is generally poor, while polyclonal EBV-LPS has had favorable responses to therapy with CD21 and CD24 monoclonal antibodies. Oligoclonal disease has not been previously reported to respond to therapy with CD21 and CD24. We report a 27-y old woman who developed a monoclonal EBV-LPS (confirmed by southern analysis of tumour for EBV DNA) after 180 mg of OKT3 for a multivisceral transplant. The patient achieved clinical remission for more than 2 months, but later died from cytomegalovirus pneumonia. Levels of CD21 and CD24 were > 2000 ng/ml during therapy and no human anti-mouse antibodies were formed. Peripheral blood B cells were cleared during therapy. We conclude that CD21 and CD24 monoclonal antibodies may be of value in the therapy of oigoclonal EBV-LPS, and merit further study.

Adult↗
PubMed1993

Sequence of Lhcb3*1, a gene encoding a Photosystem II chlorophyll a/b-binding protein in Pisum.

We have cloned and sequenced a pea Lhcb3 gene, encoding a Photosystem II chlorophyll a/b-binding protein. Sequence analysis indicates that the gene contains two introns and predicts a polypeptide of 265 amino acids. The predicted polypeptide sequence is highly homologous to the polypeptide sequences deduced from Lhcb3 genes previously characterized in tomato and barley.

Amino Acid Sequence↗
PubMed1993

Human mouse chimeric CD7 monoclonal antibody (SDZCHH380) for the prophylaxis of kidney transplant rejection.

mAb directed against CD7 have been shown to inhibit T cell proliferation in the allogeneic mixed lymphocyte reaction suggesting that CD7 may be an appropriate target for in vivo immunotherapy. We performed a prospective randomized clinical trial with a human-mouse chimeric CD7 mAb (SDZCHH380) and compared it with murine OKT3 for the prophylaxis of kidney transplant rejection. Twenty recipients of first cadaveric renal allografts were randomized to receive either SDZCHH380 or OKT3. SDZCHH380 was well tolerated. Rejection was delayed to day 35. No patients were sensitized to SDZCHH380. In contrast 7/10 OKT3 patients made anti-OKT3 antibodies. SDZCHH380 coated peripheral blood and lymph node T cells and, in contrast to OKT3, induced minimal release of IL-2, IL-6, TNF-alpha, and IFN-gamma. In addition, we showed that CD7-negative T cells mediated rejection in one of the SDZCHH380-treated patients. We conclude that the human-mouse chimeric CD7 mAb SDZCHH380 is well tolerated, is not immunogenic, and merits further study in the prophylaxis of transplant rejection.

Adolescent↗
PubMed1993

The pressor response to involuntary isometric exercise of young and elderly human muscle with reference to muscle contractile characteristics.

Changes in heart rate (fc) and blood pressure (BP) were observed in eight healthy young men aged [mean (SD)] 20 (1) years and ten healthy elderly men aged 65 (5) years, during electrically evoked contractions of the ankle plantar flexors and elbow flexors which were sustained for 2 min. There was no significant difference in the fc response to evoked contraction of the ankle plantar flexors or elbow flexors between young and elderly subjects. During contraction of the elbow flexors, elderly subjects produced an unexpectedly large rise in systolic BP which was significantly greater than that of the young subjects. The exaggerated response seen in the elderly group may be due to a more rigid arterial tree which is thought to occur with advancing age. Electrically evoked contraction of the slower contracting elderly ankle plantar flexors resulted in a significantly diminished diastolic BP response when compared with that of the young subjects. In contrast, during electrically evoked contraction of the elbow flexors, which showed a similar twitch time course in young and elderly subjects, the diastolic BP response was not significantly different between groups. This may reflect differences in the peripheral reflex input to the pressor response in elderly arm and leg muscles which, in turn, may be influenced by relative fast twitch fibre area.

Adult↗
PubMed1993

A comparison of voluntary and electrically evoked isokinetic plantar flexor torque in males.

The angle-specific isokinetic torque- and power-velocity relationships of the triceps surae were examined in ten male sprint athletes aged [mean (SD)] 22.4 (3.2) years, ten non-trained adult men aged 27.4 (4.8) years and six elderly male subjects aged 68.5 (2.4) years. Normal voluntary contractions were compared with those obtained using maximal tetanic stimulation and a release technique which standardised the level of muscle activation during isokinetic contractions. When the isokinetic data was normalized to the maximum isometric torque the stimulated release contractions at 5.18-5.29 rad.s-1 produced significantly (P < 0.05) greater torque than the voluntary no-release contractions at the same angular velocity in each group of subjects. The three subject groups generated their peak power at 3.07 rad.s-1 during the voluntary no release contractions. However, with the stimulated release contractions, power had still not reached a peak at 5.29 rad.s-1, the highest angular velocity that could be tested. It appears that at higher angular velocities the triceps surae is capable of greater torque and power generation when contractions are evoked using a stimulated release technique. It is suggested that the stimulated release technique gives a more complete picture of the torque-velocity characteristics of the contractile component of the triceps surae.

Adult↗