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Biomedical subjects

S Hall

Publications and source records attributed to S Hall.

At least 199 records · Page 11Linked to original sources

Optic axons regenerate into sciatic nerve isografts only in the presence of Schwann cells.

Optic axons regenerate into normal but not acellular peripheral nerve (PN) grafts. The first axons penetrate the PN graft before 5 days and grow inside the basal lamina tubes amongst the Schwann cells. By 30 days, 4% of the surviving retinal ganglion cells (RGC) regenerate axons for at least 10 mm into the PN graft. Laminin rich basal lamina tubes persist in the acellular PN transplants but only a few axons penetrate the most proximal parts of the tubes by 5 days and none grow farther into the graft by 30 days. RGC counts demonstrate that 34% of the normal RGC population survive 30 days after anastomosing a normal PN to the transected optic nerve. After anastomosing acellular PN grafts, 25% of RGCs survive compared with 10% after optic nerve section. These findings demonstrate that laminin does not promote regeneration of axons and that Schwann cells play the primary role of offering trophic support and even a substrate for growth. RGC survival is also enhanced by PN grafts even when Schwann cells are absent. This latter result suggests that RGC survival is promoted by a trophic substance released from axons and/or Schwann cells in the PN grafts which survives the thawing/freezing procedure (used to kill the Schwann cells) and is active in the grafts in the immediate post operative period.

Animals↗

Beta-adrenoceptors in circular and longitudinal myometrial membranes and in lung membranes from dioestrous and post-partum guinea-pigs.

1. We have examined the binding of (-)[125]-cyanopindolol ((-)[125I]-CYP) to membranes prepared from uterus and lung of dioestrous and post-partum (1-6 days) guinea-pigs. 2. The densities of beta-adrenoceptor binding sites in circular and longitudinal myometrium from dioestrous animals were similar, and approximately one-eight of those in the lung. Ascorbate and ethylenediaminetetraacetic acid in the incubation medium did not affect binding. 3. The numbers and affinities of beta-adrenoceptor binding sites in both myometrial layers and in lung parenchyma from post-partum animals were similar to those in corresponding tissues from dioestrous animals. 4. The distribution of beta-adrenoceptor binding sites in the post-partum uterus was examined using receptor autoradiography. Binding to circular and longitudinal muscle layers and to the endometrium was inhibited by (-)-propranolol (1 mumol/l), by the beta 2-adrenoceptor selective antagonist ICI 118,551 (70 nmol/l), but not by the beta 1-adrenoceptor selective antagonist CGP 20712A (100 nmol/l), indicating that the beta-adrenoceptor present was of the beta 2-subtype. 5. The ability of isoprenaline to compete for (--)[125]-CYP binding sites in uterine membranes from post-partum animals was approximately twice that in corresponding preparations from dioestrous animals. 6. Changes in the numbers or affinity of beta 2-adrenoceptors cannot account for the marked and selective enhancement of the actions of sympathomimetic amines at beta-adrenoceptors previously observed in longitudinal myometrium taken from post-partum guinea-pigs. It is suggested that enhancement of later steps in the chain of events between beta-adrenoceptor occupancy and uterine relaxation, and/or a decrease in the contribution of alpha-adrenoceptors to the net effect of the amine might provide alternative explanations.

Animals↗

Effects of adrenaline, isoprenaline and forskolin on pregnant human myometrial preparations.

1. The effects of adrenaline, isoprenaline and forskolin upon the evoked contractions of field-stimulated preparations of human, pregnant, isolated myometrium have been examined. Specimens were obtained at lower segment Caesarean section from patients at 31 (n = 1) and 36-40 (n = 10) weeks of gestation. 2. Adrenaline enhanced the electrically evoked contractions of all preparations studied, indicating that its predominant action on these pregnant myometrial tissues was at alpha- and not beta-adrenoceptors. 3. Isoprenaline in concentrations at and below 10 mumol/l produced inhibitory effects in eight of 11 experiments. In the remaining three experiments, tissues were not responsive to the inhibitory effects of isoprenaline. 4. In all preparations exposed to higher concentrations of isoprenaline (30 or 100 mumol/l), its effects were excitatory. 5. Forskolin produced inhibitory effects on preparations from all uteri, including those from which tissues unresponsive to isoprenaline had been obtained. 6. It is suggested that forskolin in the concentrations which were effective in this study produced its inhibitory effects largely through activation of adenylate cyclase. This implies that the lack of an inhibitory response of some preparations to isoprenaline was not due to reduced activity of the adenylate cyclase system, but that the failure of isoprenaline to produce an inhibitory effect could be due to diminished numbers of beta-adrenoceptors and/or increased numbers of alpha-adrenoceptors, or to a defect in the coupling of the receptors to the adenylate cyclase system. Alternatively, the presence of an endogenous antagonist of the effects of isoprenaline (for example, an eicosanoid), could mask its inhibitory effects. 7. The absence of an inhibitory effect of isoprenaline on some specimens of human gravid myometrium could have clinical implications, in view of the widespread use of beta 2-adrenoceptor agonists as uterine relaxants.

Adenylyl Cyclases↗

Neuropsychiatric manifestations of systemic lupus erythematosus.

Forty-six episodes of major neuropsychiatric manifestations of systemic lupus erythematosus occurring in 35 patients over a ten-year period were reviewed. The frequency of central nervous system SLF was lower than that reported from overseas referral centres. Glucocorticosteroid treatment did not precipitate psychiatric problems in this group. Whilst neuropsychiatric recovery was the rule, such features indicated a subgroup of SLE with high short-term mortality.

Adolescent↗

Kinetic basis for insensitivity to tetrodotoxin and saxitoxin in sodium channels of canine heart and denervated rat skeletal muscle.

The single-channel blocking kinetics of tetrodotoxin (TTX), saxitoxin (STX), and several STX derivatives were measured for various Na-channel subtypes incorporated into planar lipid bilayers in the presence of batrachotoxin. The subtypes studied include Na channels from rat skeletal muscle and rat brain, which have high affinity for TTX/STX, and Na channels from denervated rat skeletal muscle and canine heart, which have about 20-60-fold lower affinity for these toxins at 22 degrees C. The equilibrium dissociation constant of toxin binding is an exponential function of voltage (e-fold per 40 mV) in the range of -60 to +60 mV. This voltage dependence is similar for all channel subtypes and toxins, indicating that this property is a conserved feature of channel function for batrachotoxin-activated channels. The decrease in binding affinity for TTX and STX in low-affinity subtypes is due to a 3-9-fold decrease in the association rate constant and a 4-8-fold increase in the dissociation rate constant. For a series of STX derivatives, the association rate constant for toxin binding is approximately an exponential function of net toxin charge in membranes of neutral lipids, implying that there is a negative surface potential due to fixed negative charges in the vicinity of the toxin receptor. The magnitude of this surface potential (-35 to -43 mV at 0.2 M NaCl) is similar for both high- and low-affinity subtypes, suggesting that the lower association rate of toxin binding to toxin-insensitive subtypes is not due to decreased surface charge but rather to a slower protein conformational step. The increased rates of toxin dissociation from insensitive subtypes can be attributed to the loss of a few specific bonding interactions in the binding site such as loss of a hydrogen bond with the N-1 hydroxyl group of neosaxitoxin, which contributes about 1 kcal/mol of intrinsic binding energy.

Animals↗

Calcium and the Fc receptor on human platelets.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 10(7) to 10(8) L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects. At 4 degrees C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

Blood Platelets↗

Ownership and performance: the case of outpatient mental health clinics.

Policy analysts and researchers have been concerned with the growth and impact of for-profit institutions providing health care services. Research results to date have been mixed on the effect of ownership on quality and cost to payers. Equivocal findings may be due, in part, to measurement limitations inherent in facility-level data. This study reports results from a homogeneously insured population receiving outpatient mental health care at proprietary and nonprofit clinics. Data are claims on behalf of 30,000 covered individuals served at 223 clinics. Controls for case mix and other variables permit isolation of the impact of form of ownership. Using regression analysis, the authors find that payments to proprietary clinics exceeded payments to private nonprofit clinics by 27%, public clinics by 19%, and religious clinics by 17%. All differences were significant. This finding suggests that proprietary clinics are on average more commercially oriented than nonprofit facilities.

Health Facilities, Proprietary↗

Relationship between decay accelerating factor deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes.

Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes exhibit abnormalities in decay accelerating factor (DAF), acetylcholinesterase, and resistance to autologous C5b-9 attack. To investigate the nature of the lesion underlying PNH cells, we examined the relationship of these abnormalities to one another. Analyses of DAF in acetylcholinesterase-negative erythrocytes revealed that these two abnormalities involve functionally independent molecules, coincide precisely in the same cell populations, and are similarly expressed in PNH II and more complement-sensitive PNH III erythrocytes. The DAF and acetylcholinesterase deficiencies contrast with the C3b/C4b receptor (CR1) deficit, which is less profound and similarly distributed in complement-insensitive cell populations. Hemolytic studies showed that defective resistance to autologous C5b-9 attack is mediated by another mechanism. Whereas reconstitution of PNH II erythrocytes with DAF completely corrected their complement sensitivity, DAF reconstitution of PNH III erythrocytes restored their ability to circumvent C3b uptake but had no effect on their heightened susceptibility to reactive lysis. Assays of complement-insensitive (PNH I) erythrocytes surviving after reactive lysis disclosed partial DAF and acetylcholinesterase deficits. These findings indicate that the PNH lesion involves multiple membrane components and that PNH I erythrocytes are also abnormal.

Acetylcholinesterase↗

Halothane anesthesia decreases human monocyte hydrogen peroxide generation. Protection of monocytes by activation with gamma interferon.

In an effort to determine the impact of halothane anesthesia on certain human cell-mediated immune functions, normal, purified human monocytes and lymphocytes were exposed to halothane in vitro at varying concentrations for up to 8 hours. Subsequently, these human effector cells were analyzed for their ability to function in several cell-mediated immunologic assays. Natural killer cell activity against K-562 was unaffected by halothane in most of the donors tested. Similarly, the ability of purified monocytes to inhibit MBL-2 tumor cell growth was unchanged. Halothane appeared to decrease the proliferative response of lymphocytes to phytohemagglutinin (PHA) in approximately 50% of the normal donors tested. In contrast, the ability of monocytes to lyse antibody-coated red cell targets (ADCC) was unaffected by even maximal exposure to halothane. Of interest was the finding that human monocytes exposed to as low as 2% halothane anesthesia for 4 hours displayed a dramatic down-regulation of hydrogen peroxide (H2O2) release. Since it is known that hydrogen peroxide and other incompletely reduced forms of oxygen secreted by monocytes can play a major role in the antimicrobial, antitumor, and inflammatory functions of these cells, this finding may help explain the enhanced susceptibility of post-operative patients to infections.

Adult↗

Severe visceral disease in subacute cutaneous lupus erythematosus.

Subacute cutaneous lupus erythematosus has been heralded as a marker of relatively benign subset of systemic lupus erythematosus. In this article, we describe two cases with severe visceral disease and suggest that it may be less reliable as a predictor of benign disease than was previously accepted.

Adult↗

Reduced tar, nicotine, and carbon monoxide exposure while smoking ultralow- but not low-yield cigarettes.

An unresolved public health issue is whether some modern cigarettes are less hazardous than others and whether patients who cannot stop smoking should be advised to switch to lower-yield cigarettes. We studied "tar" (estimated by urine mutagenicity), nicotine, and carbon monoxide exposure in habitual smokers switched from their usual brand to high- (15 mg of tar), low- (5 mg of tar), or ultralow-yield (1 mg of tar) cigarettes. There were no differences in exposure comparing high- or low-yield cigarettes, but tar and nicotine exposures were reduced by 49% and 56%, respectively, and carbon monoxide exposure by 36% while smoking ultralow-yield cigarettes. Similarly, in 248 subjects smoking their self-selected brand, nicotine intake, estimated by blood concentrations of its metabolite cotinine, was 40% lower in those who smoked ultralow but no different in those smoking higher yields of cigarettes. Our data indicate that ultralow-yield cigarettes do deliver substantial doses of tar, nicotine, and carbon monoxide, but that exposures are considerably less than for other cigarettes.

Adult↗

The effect of anesthetic agents on human immune system function. I. Design of a system to deliver inhalational anesthetic agents to leukocyte cultures in vitro.

A novel system for exposing purified human mononuclear leukocyte subsets or any cultured cell to inhalational anesthetic agents has been devised. Monocytes and lymphocytes are purified by counter-current centrifugal elutriation and put into culture vessels with and without appropriate functional activators. The culture vessels are placed into one of four anesthetic agent exposure chambers, each containing a different concentration of the anesthetic agent to be tested. The system that delivers the anesthetic agent to the culture vessels is essentially the same as the one used in the operating room; the actual levels of anesthetic agent delivered are monitored. In this report, we present evidence that halothane can be successfully tested using the above-cited experimental design; this agent substantially inhibits the secretion of interferon by human mononuclear cells. The ability of monocytes to secrete alpha interferon in response to polyinosinic: polycytidylic acid (poly I:C) was significantly depressed following 4 h in vitro exposure to increasing concentrations of halothane; the secretion of gamma interferon by lymphocytes in response to phytohemagglutinin (PHA) was also depressed, although to a lesser degree. The system presented should allow for the in vitro exploration of the effects of inhalational agents on purified human leukocyte subset functions as well as for the analysis of the effect of these agents on monocyte/lymphocyte interactions.

Halothane↗

The painful swollen calf. A comparative evaluation of four investigative techniques.

Complications of popliteal cysts may closely mimic the clinical features of a deep venous thrombosis. We assessed the sensitivity and specificity of the non-invasive procedures of radionuclide venography and popliteal space ultrasound examination compared with those of contrast venography and arthrography, respectively, and then prospectively studied 23 non-surgical patients with acutely painful, swollen calves to determine the utility of these techniques. The cause of this symptom was popliteal cyst complications in 10 patients, deep venous thrombosis in seven patients, and both conditions in two patients. Radionuclide venography was highly reliable and ultrasound examination was specific but only moderately sensitive in these studies. The painful, swollen calf may be investigated adequately in most cases by means of noninvasive invasive techniques; contrast venography and arthrography should be reserved for only a minority of patients.

Adult↗