PubMed HealthSearch

Biomedical subjects

K Nash

Publications and source records attributed to K Nash.

12 recordsLinked to original sources

Antibodies to soluble human T cell receptor beta chain recognize multiple epitopes on cell surface TcR.

The T cell receptor (TcR) is an integral membrane protein occurring as a disulfide linked heterodimer, non-covalently associated with CD3 on the surface of T lymphocytes. Antibodies to the TcR have been shown to be effective for treating autoimmune disorders in animals. We describe here a method for producing antibodies to cell surface determinants of the human TcR, using a soluble form of the receptor as antigen. Soluble V alpha 1.2, V beta 8.1, V beta 11 TcR chains are expressed from a construct in which the extracellular domains of the TcR are fused to the mouse gamma 2a heavy chain constant region lacking the CH1 domain. These chimeric molecules contain both immunoglobulin and TcR determinants, as revealed by antibody probes. Amino-terminal sequence analysis of a chimeric V beta 8.1 molecule indicates that the TcR leader peptide is correctly processed from the soluble form. Antibodies raised against the soluble human V beta 8.1 molecule recognize the native determinants on Jurkat cells, and on natural T cells derived from resting human peripheral blood lymphocytes. Epitope mapping studies using competitive binding assays suggest that the anti-V beta 8 antibodies produced using soluble antigen recognize multiple overlapping determinants on the cell surface form of the TcR.

Amino Acid Sequence

Evidence that the hypothermic response of mice to delta-9-tetrahydrocannabinol is not mediated by changes in thermogenesis in brown adipose tissue.

Delta 9-Tetrahydrocannabinol (20 mg/kg i.p.) and propranolol (20 and 50 mg/kg i.p.) produced marked falls in the rectal temperatures of mice kept at an ambient temperature of 22 degrees C. Propranolol (50 mg/kg i.p.) also decreased the thermogenic activity of brown fat, as measured by a decrease in the level of [3H]GDP binding to mitochondria obtained from mouse interscapular brown adipose tissue. In contrast, delta 9-tetrahydrocannabinol (20 mg/kg i.p.) did not affect mitochondrial GDP binding even though the dose used was one shown previously to depress heat production. GDP binding was also unaffected by this cannabinoid in brown adipose tissue taken from mice that had been kept at 13 degrees C instead of 22 degrees C. In mice kept at 34 degrees C, isoprenaline (0.25 and 1.0 mg/kg s.c.) induced a marked rise in rectal temperature and increased the level of GDP binding to brown fat mitochondria. Propranolol (50 mg/kg i.p.) prevented the hyperthermic response to isoprenaline, the mice becoming hypothermic instead. Delta 9-Tetrahydrocannabinol (20 mg/kg i.p.) had no effect on isoprenaline-induced hyperthermia. We conclude from these data that there is no significant involvement of brown adipose tissue in the hypothermic response of mice to delta 9-tetrahydrocannabinol.

Adipose Tissue

A randomized trial of Veterans Administration home care for severely disabled veterans.

This randomized study screened hospital admissions to all wards except Psychiatry and Spinal Cord Injured during a 3-year period to identify 233 severely disabled patients (2 impairments on the Katz Index of ADL) and caregivers who were willing to participate in a pretest-multiple posttest trial of the Hines VA Hospital-based Home Care (HBHC) Program. Patient functional status, morale, and satisfaction with care were measured at baseline, 1 month and 6 months post discharge. Caregiver satisfaction and morale were assessed at the same time periods. All health care services used by both groups were tracked over the 6-month period and converted to cost. Findings include improved 1-month satisfaction with care (P = 0.04) and improved 6-month cognitive functioning (P = 0.04) among HBHC patients and improved 1-month (P = 0.04) and 6-month satisfaction with care (P less than 0.01) among their caregivers. A nonsignificant 10% decrease in net cost of care, was found in the treatment group, largely due to lower use of private sector hospital care.

Aftercare

Cost-effectiveness of Veterans Administration hospital-based home care. A randomized clinical trial.

A randomized design was used to examine the cost-effectiveness of a Veterans Administration hospital-based home care program that case managed inpatient and outpatient care. Patients (N = 419) with two or more functional impairments or a terminal illness were randomized to hospital-based home care (n = 211) or customary care (n = 208). Functional status, satisfaction with care, and morale were measured at baseline and at 1 and 6 months after discharge from the hospital; health care utilization was tracked for 6 months. Findings included significantly higher (0.1 on a three-point scale) patient and caregiver satisfaction with care at 1 month and lower Veterans Administration and private sector hospital costs ($3000 vs $4245) for the experimental group. Net per person health care costs were also 13% lower in the experimental group. We conclude that this model of hospital-based home care is cost-effective and that its expansion to cover these two patient groups throughout the Veterans Administration system can improve patient care at no additional cost.

Aged

Monoamine oxidase inhibitor update. Potential adverse food and drug interactions.

Monoamine oxidase inhibitors (MAOIs) are medicines with potential for therapeutic gains, but they may also have adverse consequences. The risk: benefit ratio is assessed and, in appropriately selected cases, efficacy should outweigh disadvantages. Hypotension is the most prominent side-effect; yet the primary concern in the MAOI-treated person is to prevent co-exposure to substances with indirectly-acting sympathomimetic properties. Such co-utilisations from certain foods or drugs can result in dangerous hypertensive and hyperpyretic crises. A responsible individual should be involved in the administration of these drugs. The patient and family must fully understand the self-discretionary diet avoidance rules, which stress abstinence from high-tyramine foods. Drug prohibitions also emphasise elimination of indirect action sympathomimetics, but all pharmaceutical applications are always strictly controlled by the well informed physician who prescribes MAOIs. Treatment of the hypertensive crisis is urgent and includes alpha-blockade. Overdoses require supportive therapies and may necessitate acidification of the urine.

Drug Interactions