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Biomedical subjects

M Holland

Publications and source records attributed to M Holland.

18 recordsLinked to original sources
PubMed1992

W-7, a calmodulin antagonist, and contracture of malignant hyperthermia susceptible skeletal muscle.

1. In malignant hyperthermia susceptible muscle fibers, the calmodulin antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%) induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene sodium (6 microM) prevented and reversed W-7 induced contracture: nifedipine did not. 3. In chemically skinned fibers, 10 microM, 1.0 microM, and 0.1 microM W-7 released 100%, 30%, and 10% of stored calcium respectively, and the effect of 10 microM W-7 was irreversible in that the SR was unable to re-sequestor calcium after exposure to the drug. 4. The release of calcium by W-7 was not prevented by exogenously added calmodulin (3 microM), nor mimicked by mastoparan (10 microM). 5. Calcium release by W-7 appears to be independent of calmodulin inhibition.

Animals↗
PubMed1992

Altered mechanical responses of malignant hyperthermic skeletal muscle during repetitive stimulation.

This investigation examined the mechanical responses of malignant hyperthermic (MH) and normal porcine skeletal muscle to repetitive stimulation. Twitch and maximal tetanic tensions were not significantly different between muscle types. Tensions produced during stimulation at 20-80 Hz were significantly less in MH muscle than in normal muscle. In addition, MH muscle showed significantly greater force decline (tetanic fade) at the end of contractions evoked by 20-80 Hz stimulation. When stimulated to fatigue, both normal and MH muscle exhibited similar rates of tension decline during the initial minutes. Further stimulation caused additional decline in normal muscle, but a tension plateau in MH muscle. In all cases, normal muscle had greater magnitudes of fatigue than did MH muscle. Results show that there are marked differences between MH and normal muscle in the mechanical responses to repetitive stimulation. Due to its inability to properly regulate intracellular Ca2+ exchange, it is possible that MH muscle might be a useful tool for identifying the mechanisms of muscle fatigue in normal muscle.

Animals↗
PubMed1992

Synergistic effects of oral nonsteroidal drugs and topical corticosteroids in the therapy of sunburn in humans.

The ability to modify skin injury due to ultraviolet light (UVB) by the nonsteroidal anti-inflammatory drugs (NSAIDs) oral ibuprofen (IB) or indomethacin (IN) plus topical betamethasone dipropionate (BD) was studied in 24 subjects in this open-label, four-way, cross-over trial. All subjects received UVB at weekly intervals: group 1 was randomized to IB, BD, IB + BD or control, and group 2 to IN, BD, IN + BD or control. Oral medications were given prior to and after exposure to UVB, but BD was applied only afterwards. The skin response to UVB [erythema and increased skin blood flow (SBF)] was measured serially for 96 h. A skin biopsy was taken at 24 h after each dosing with UVB. At maximum erythema (8-12 h after UVB), the following approximate reductions in SBF (compared to control responses) were noted: 42-58% for combination therapies, 33-40% for IB or IN alone, and 17% for BD alone. SBF tended to equalize across all treatments by 24 h and remained until 96 h. Skin biopsy results were consistent with the noninvasive findings. Thus, we observed a synergistic effect of reduction of UVB-induced erythema and SBF with combinations of oral NSAIDs and topical corticosteroids. This study could have implications for the therapy of sunburn in humans.

Administration, Oral↗
PubMed1992

Na(+)-Ca2+ exchange influences halothane and caffeine contractures of malignant hyperthermic skeletal muscle.

These experiments sought to determine the influence of sarcolemmal Na(+)-Ca2+ exchange on halothane and on caffeine contractures of malignant hyperthermic (MH) skeletal muscle. Fiber bundles excised from MH susceptible pigs (Pietrain) were exposed to halothane (3%) and caffeine (0.5-8.0mM) while Na(+)-Ca2+ exchange was inhibited by reducing extracellular Na+ from 100% to 50, 25 and 0% of control. Halothane contracture magnitude was not altered by 50 or 25% Na+ whereas 0% Na+ increased the contractures by 51%. 0 and 25% Na+ increased the magnitude of caffeine contractures (2-8mM) by 53-176%. These results suggest that external Na+ and the Na(+)-Ca2+ exchange mechanism influences contractures of MH skeletal muscle.

Animals↗
PubMed1991

Homeostatic action of interleukin-4 on endogenous and recombinant interleukin-2-induced activated killer cell function.

Cytokine-secreting, major histocompatibility complex-unrestricted activated killer (AK) cells are toxic to a wide range of virus-infected or malignant target cells and may be generated endogenously, eg, after bone marrow transplantation, or by infusion of cytokines such as recombinant interleukin-2 (rIL-2). Although AK cells secrete cytokines such as gamma-interferon and tumor necrosis factor, which are themselves able to recruit fresh cytokine-secreting AK cells, activation in both settings is short-lived, implying the existence of homeostatic regulatory mechanisms. We now demonstrate one mechanism by which rapid homeostasis is achieved. We show that IL-4 is produced in patients with both endogenously and exogenously generated AK cells. The cytokine was detected in serum after marrow transplantation, and IL-4 transcripts appeared in circulating lymphocytes during rIL-2 infusion. Although IL-4 inhibited the induction phase of AK cell function, it had no significant inhibitory effect on the ability of AK cells from these individuals to respond to restimulation. Nonetheless, neutralization of the IL-4 induced during cell activation doubled the half-life of AK function, once activating stimuli were removed, from 18 to 44 hours and produced a 2-log increase in AK cell secretion of tumor necrosis factor and gamma-interferon. These data suggest that IL-4 induced in vivo during lymphocyte activation abbreviates AK cell responses once the triggering stimuli have been removed. Neutralization of endogenous IL-4 in vivo by appropriate monoclonal antibodies might prolong the duration of AK function.

Bone Marrow Transplantation↗
PubMed1991

BAY K 8644 and nifedipine alter halothane but not caffeine contractures of malignant hyperthermic muscle fibers.

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Effects of BAY K 8644, nifedipine, and low Ca2+ on halothane and caffeine potentiation.

The purpose of this investigation was to examine the effects of the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine on halothane- and caffeine-induced twitch potentiation of mammalian skeletal muscle. Muscle fiber bundles were taken from normal Landrace pigs and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), and low Ca2+ media administered alone and in combination with halothane (3%) or with increasing concentrations of caffeine (0.5-8.0 mM). Both BAY K 8644 and halothane potentiated twitches by approximately 80%; when they were administered in combination, twitch potentiation was nearly double that caused by either drug alone. In the presence of nifedipine, halothane increased twitches by less than 30%. Low Ca2+ significantly depressed twitches by approximately 25% but also inhibited halothane's inotropic effect. BAY K 8644 augmented caffeine potentiation but only at low caffeine concentrations (0.5-2.0 mM). Nifedipine and low Ca2+ failed to inhibit caffeine's inotropic effects. These results suggest that halothane potentiates twitches via a mechanism that involves or is influenced by extracellular Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Lack of sex differences with the Baldwin illusion.

Responses of college students (16 men and 16 women) to the Baldwin illusion showed a significant effect for size of square but not for sex. Findings are consistent with those reported previously by Porac, Coren, Girgus, and Verde for adults and for the oldest group of children tested by Pressey and Wilson.

Adult↗
PubMed1990

Effects of the calcium antagonist, TMB-8 on halothane and on caffeine contractures of malignant hyperthermia susceptible skeletal muscle.

This investigation sought to determine if the Ca2+ antagonist, TMB-8, alters the contracture responses of malignant hyperthermia susceptible (MHS) skeletal muscle to halothane and to caffeine. Muscle fiber bundles were excised from both MHS and normal pigs and exposed to TMB-8 (100 microM), halothane (3%) and caffeine (0.5-8.0 mM), administered alone and in combination. TMB-8 depressed tension developed during isometric twitches in both MHS and normal muscle but had no effect on resting tension (RT). Halothane, however, increased RT in MHS but not in normal muscle. TMB-8 failed to reduce the halothane contracture of MHS muscle but hastened its onset. Caffeine concentrations of greater than or equal to 2 mM increased RT in MHS whereas only 8 mM evoked contracture of normal muscle. These effects were also unaltered by TMB-8. Results suggest that TMB-8 does not inhibit halothane nor caffeine contractures of MHS muscle.

Animals↗
PubMed1989

Effect on yeast LEU2 expression of upstream activation sequence from yeast ENO2 gene coding for enolase.

The upstream activation sequence from ENO2, one of two genes coding for yeast enolase, was inserted into the upstream 405 HpaI site of LEU2, which codes for beta-isopropylmalate dehydrogenase (E.C. 1.1.1.85), utilizing shuttle plasmid YEp13. The effect of the ENO2 upstream activation sequence on expression of yeast LEU2 was studied. Our results revealed a fourfold increase in expression for LEU2 in both orientations after activation by the ENO2 upstream activation sequence. Leucine repressed LEU2 expression. Glucose did not induce the ENO2 upstream activation sequence effect on LEU2 expression. It is possible to construct a high-level expression system in yeast by using the ENO2 upstream activation sequence.

3-Isopropylmalate Dehydrogenase↗
PubMed1988

[Function and morphology of intraperitoneal segmental pancreas allotransplants with cyclosporin monotherapy in the dog--a comparison of 4 drainage procedures of exocrine secretions].

Dogs which had received cyclosporine A for immunosuppression were investigated to elucidate functionality and morphological alterations in pancreas allografts, with enteral, vesical, peritoneal or occluded exocrine drainage. None of the animals with enteral drainage survived the first four postoperative weeks, with lethal infections being responsible for allograft failure. Full functionality three months from transplantation was recorded from three of seven transplants with ductal occlusion and unobstructed drainage into the abdominal cavity. Ductal occlusion was repeatedly accompanied by pancreatitis and pseudo-cysts. Fibrotisation of the organ and loss of endocrine islets of pancreas were recordable from these cases just as from grafts with unobstructed drainage into the abdominal cavity. Drainage of exocrine secretion into the bladder yielded good success in one of seven animals and was morphologically and functionally characterised primarily by occlusive metaplastic ossification along the transition to the anastomosis.

Animals↗
PubMedDate not supplied

Program accountability survey.

The public more and more is demanding accountability from its government agencies, professional bodies, and service areas. To address the accountability of a radiologic technology program in terms of its students, a questionnaire has been developed to send to them a year after they graduate. The responses are valuable in anticipating manpower needs, writing behavioral objectives, adjusting curriculums to meet changing needs, and responding to governamnet and accrediting agencies.

Evaluation Studies as Topic↗