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Biomedical subjects

J Abraham

Publications and source records attributed to J Abraham.

At least 19 recordsLinked to original sources

Basic fibroblast growth factor mediates its effects on committed myeloid progenitors by direct action and has no effect on hematopoietic stem cells.

Basic fibroblast growth factor or fibroblast growth factor-2 (FGF) has been shown to affect myeloid cell proliferation and hypothesized to stimulate primitive hematopoietic cells. We sought to evaluate the effect of FGF on hematopoietic stem cells and to determine if FGF mediated its effects on progenitor cells directly or through the induction of other cytokines. To address the direct effects of FGF, we investigated whether FGF induced production of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, IL-6, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor by two types of accessory cells, bone marrow (BM) fibroblasts and macrophages. We further evaluated whether antibodies to FGF-induced cytokines affected colony formation. To determine if FGF was capable of stimulating multipotent progenitors, we assessed the output of different colony types after stimulation of BM mononuclear cells (BMMC) or CD34+ BMMC and compared the effects of FGF with the stem cell active cytokine, kit ligand (KL). In addition, a subset of CD34+ BMMC with characteristics of hematopoietic stem cells was isolated by functional selection and their response to FGF was evaluated using proliferation, colony-forming, and single-cell polymerase chain reaction (PCR) assays. We determined that FGF had a stimulatory effect on the production of a single cytokine, IL-6, but that the effects of FGF on colony formation were not attributable to that induction. FGF was more restricted in its in vitro effects on BM progenitors than KL was, having no effect on erythroid colony formation. FGF did not stimulate stem cells and FGF receptors were not detected on stem cells as evaluated by single-cell reverse transcription PCR. In contrast, FGF receptor gene expression was detected in myeloid progenitor populations. These data support a directly mediated effect for FGF that appears to be restricted to lineage-committed myeloid progenitor cells. FGF does not appear to modulate the human hematopoietic stem cell.

Adipose Tissue

Volatile anesthetics and glutamate activation of N-methyl-D-aspartate receptors.

Several studies have indicated important functional interactions between volatile anesthetics and the N-methyl-D-aspartate (NMDA) class of glutamate receptors. In the present study, we examined the effects of diethyl ether, chloroform, methoxyflurane, halothane, enflurane, and isoflurane on (1) glutamate activation of the NMDA receptor complex, including glycine reversal of anesthetic action, as revealed by [3H]-(5R, 10S)-(+)methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine, dizocilpine (MK-801) binding to the cation channel, and (2) [3H]cis-4-( phosphonomethyl)piperidine-2-carboxylic acid (CGS 19755) binding to the glutamate recognition site of the NMDA receptor In agreement with previous studies, glutamate increased the binding of 1 nM [3H]MK-801, measured after a 1-hr incubation at 37 degrees, by up to several hundred fold. This stimulation was blocked by glutamate antagonists and potentiated by glycine with an EC50 of approximately 0.03 muM. Glycine also had a direct stimulatory effect on [3H]MK-801 binding at much higher concentrations ( > or = 10 muM). All of the anesthetics examined depressed glutamate stimulation of [3H]MK-801 binding in a concentration-dependent manner with the following order of potency: halothane > or = enflurane > methoxyflurane > chloroform > diethyl ether. This inhibition of [3H]MK-801 binding was observed at concentrations that are routinely attained in the cerebrospinal fluid during surgical anesthesia. Moreover, the inhibition was reversed rapidly following removal of the anesthetics from the assay medium. Inclusion of glycine in the incubation medium markedly attenuated anesthetic-induced inhibition of glutamate-sensitive [3H]MK-801 binding with an EC50 of between 0.1 and 1 muM. Thus, this reversal by glycine correlated with its potentiating as opposed to its direct stimulatory, effect on NMDA receptors. Anesthetic inhibition of [3H]MK-801 binding could not be overcome by raising the glutamate concentration (i.e. the interaction did not appear to be competitive with respect to glutamate) unless glycine was present. Binding of [3H]CGS 19755 to the glutamate recognition site was also inhibited by each of the anesthetics examined. However, with the exception of chloroform, all of the anesthetics were more potent inhibitors of glutamate-stimulated [3H]MK-801 binding than they were of [3H]CGS 19755 binding. [3H]CGS 19755 binding saturation curves in the presence of halothane and enflurane indicated a decrease in the density of [3H]-CGS 19755 binding sites with no change in binding affinity (i.e. the inhibition did not appear to be competitive). These findings support the idea that anesthetic drugs disrupt NMDA receptor transmission through multiple allosteric effects on the receptor-channel activation mechanisms and the glutamate binding site.

Anesthetics, Inhalation

Renal and renin responses to furosemide in conscious lambs during postnatal maturation.

Despite the widespread use of furosemide in the treatment of various fluid and electrolyte disorders in the preterm and term human infant and child, the physiological effects of this potent diuretic agent on renal function and renin release during postnatal maturation are poorly understood. To test the hypothesis that the renal and renin responses to furosemide are altered during postnatal maturation, experiments were carried out in conscious chronically instrumented newborn lambs (11 +/- 3 days, n = 7) and older lambs (28 +/- 3 days, n = 6), at least 5 days after surgery under halothane anesthesia for placement of catheters. Renal function and plasma renin activity (PRA) were measured for 1 h before and 2 h after intravenous injection of furosemide (2 mg/kg; 0.2 mL/kg) or vehicle (0.2 mL/kg). Glomerular filtration rate (GFR) decreased after furosemide administration to both groups of lambs. However, the time course of this decrease in GFR was different, occurring sooner in older lambs (30 min) than in newborns (90 min). GFR remained significantly decreased after 150 min in both age-groups. The natriuretic and diuretic responses to furosemide were similar in newborns and older lambs, peak diuretic and natriuretic responses occurring within 30 min. PRA increased dramatically in both age-groups after furosemide; the response was accentuated in newborns. After 2 h, PRA was still elevated in newborns but returned towards control levels in older lambs. These data demonstrate that both the GFR and renin responses to furosemide are altered during ontogeny.

Animals

The production and reception of scientific papers in the academic-industrial complex: the clinical evaluation of a new medicine.

The production and reception of scientific papers in the academic-industrial complex have been neglected in sociology. In this article the social processes which influence the nature of the scientific paper in that complex are explored in depth by taking a number of controversial medical papers as case studies. The empirical evidence is collected and discussed in the light of sociological theories of normative ethos, paradigm development, reward-induced conformity and social interests in science. It is concluded that within the medical-industrial complex conformity to industrial interests can be a major criterion in defining the kind of reception given to a scientific paper and the professional autonomy of the authors in the paper's production, rather than an ethos of scientific scepticism or commitment to paradigmatic conventions. This is seen to have implications for the production of scientific knowledge - implications that might be in conflict with the public interest. Consequently, the desirability of current British Government proposals to intensify its policy of making science more responsive to the needs of industry may have significant drawbacks, hitherto unacknowledged in official circles, and in need of more extensive sociological investigation.

Clinical Trials as Topic

Thyroid disease and abnormal thyroid function tests in women with eating disorders and depression.

Forty-two female patients with an eating disorder and major depression were compared with 48 female patients with major depression in a retrospective chart study for the prevalence of thyroid disease and laboratory thyroid function abnormalities in the absence of thyroid disease. Eating disorder patients, aged 30-80 years, had a significantly higher incidence in thyroid diseases (53%) then those with major depression alone (17%). The incidence of thyroid disease did not differ between the two groups among patients aged 11-29 years. Abnormal thyroid screening values occurred in 40% of euthyroid eating disorder patients and 34% of those with major depression. While the overall prevalence of thyroid disease in depressed females (15%) was similar to that in the general population (10.5%), thyroid disease in the eating disordered/depressed patients was twice the rate expected (24%) in the general population. Female patients who require psychiatric hospitalization should be routinely evaluated for thyroid function, especially those diagnosed with an eating disorder and depression.

Adolescent

Modulation of megakaryocytopoiesis by human basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) may act to modulate hematopoiesis in addition to its effects on mesenchymal cells. We studied the effects of bFGF on human and murine primary marrow megakaryocytes. bFGF modestly enhanced the size of the human megakaryocyte colony-forming unit (CFU-MK) and cell numbers per colony, in combination with interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF). Adhesion of human megakaryocytes to bone marrow (BM) stromal fibroblasts was enhanced when either stromal fibroblasts or megakaryocytes were treated with bFGF. This resulted in significantly increased proliferation of megakaryocytes. In addition, bFGF augmented secretion of the cytokines tumor necrosis factor alpha and IL-6 by human primary BM megakaryocytes. Immature murine megakaryocytes showed a significant growth response to bFGF as measured by the single cell growth assay. This effect was abrogated by specific antibodies for bFGF and combination of anti-IL-6 and anti-IL-1 beta antibodies. bFGF has no effect on murine CFU-MK formation, but significantly potentiated CFU-MK formation in the presence of IL-3 or GM-CSF. These results indicate that the effect of bFGF on various megakaryocyte populations is different and that bFGF may affect megakaryocytopoiesis via modulation of megakaryocyte-stromal interactions and via augmentation of cytokine secretion from megakaryocytes.

Animals

Athermal physiological effects of microwaves on a cynobacterium Nostoc muscorum: evidence for EM-memory bits in water.

Athermal physiological effects of continuous wave and modulated microwaves were studied on a cynobacterium Nostoc muscorum. The study shows that different microwave frequencies in continuous wave and modulated modes produced significantly different physiological effects on the algae. Water-mediated bioeffects further present additional proof that water has the capability to remember the imposed electromagnetic field characteristics for an extended period of time.

Culture Media

Microvascular morphometry in primate diaschisis.

Focal cerebral ischemia was produced in monkeys by transorbital occlusion of the right middle cerebral artery. Following this, in one group of animals the total microvasculature, including both perfused and nonperfused vessels of the opposite caudate nucleus and insula, was examined by alkaline phosphatase staining of the endothelium. In another group, the patency of the microvascular bed was visualized by india ink perfusion. The number, diameter, and length of visualized vessels were measured by means of a Wild ASBA image analysis system. The perfused patient microvascular bed was significantly reduced in both insula and caudate nucleus in the supposedly normal left side, although the total microvascular volume showed an increase at 4 and 12 hr in the insula and at 48 hr in the caudate nucleus. Reduced perfusion in the hemisphere opposite to the occluded middle cerebral artery provides an anatomical substrate for the phenomenon of "diaschisis."

Animals

Assessment of buccal separators in the relief of bruxist activity associated with myofascial pain-dysfunction.

The purpose of this study was to evaluate the effectiveness of heavy (S2) Alastik separators in relieving bruxist activity as monitored through masseter muscle area EMG activity, muscle palpation, and self-reporting in 21 Caucasian subjects. The subjects, all of whom suffered from both bruxism and myofascial pain-dysfunction, were randomly assigned to one of three groups: experimental (separator group); placebo (separator placed and removed); and control groups (no separator). The findings from this study indicate that there were no observable differences in either subjective or objective responses to the pretreatment versus posttreatment questionnaire and clinical examination for tooth clenching or grinding, facial pain, and fatigue of the jaws. In addition, no statistical differences were found between pre and posttreatment data. The EMG data did not show any statistical differences between pretreatment and posttreatment evaluations or among the 3 groups.

Adult

Stenosis of the axis and cervical myelopathy. Case report.

A rare case is described of marked segmental stenosis of the axis secondary to developmental hypertrophy of the posterior neural arch causing cervical myelopathy. The patient made a remarkable recovery following decompressive laminectomy.

Adult

Evaluation of drug effects on spinal cord injury--an experimental study in monkeys.

Contusion injury is produced experimentally in anaesthetised monkeys by weight drop method. A group of animals having laminectomy alone served as sham controls. Drugs were administered 30 min after injury initially. Naloxone and nifedipine were administered as single dose administration immediately after injury. Dipyridamole and DMSO were administered daily for a period of 1 week. Acetylcholinesterase (AchE) was estimated in 2 spinal tissue segments, S1-at the site of injury and S2-the segment above the site of injury, at the end of 1 week after sacrificing the animals. Contusion injury produced significant decrease in specific activity of AchE in the traumatised segment of the experimental animals. The non-traumatised adjacent segment did not show any significant change. Nifedipine, naloxone and DMSO produced a decrease in AchE activity in S1 and S2 segments. Monkeys developed paraplegia after contusion injury. A score 2+ was observed after 1 week as compared to the score of 4+ of sham controls. Single dose administration of naloxone seemed to reverse the motor deficit by getting a score of 3+; other drugs did not produce any beneficial effect on motor deficit.

Animals

Single small enhancing CT lesions in Indian patients with epilepsy: clinical, radiological and pathological considerations.

Thirty consecutive Indian patients with focal or generalised seizures and single, small (less than 10 mm), enhancing lesions on CT scans (SSECTL) were studied. Five patients (Group A) were treated with anticonvulsants alone and did not have a biopsy. In ten patients (Group B) a CT guided stereotaxic biopsy of the lesion was carried out and in the remainder (15-Group C) and excision biopsy of the lesion was carried out following CT guided stereotaxic localisation. In all patients in Group B the lesion were reported as "chronic nonspecific inflammation". In seven of 15 patients in Group C the lesions showed a cysticercus with a granuloma and in a further five the pathology was that of a "parasitic granuloma" but the parasite could not be identified. Biopsy did not reveal a tuberculoma or neoplasm in any of the patients. The lesions studied are the same as "disappearing" CT lesions reported in Indian patients, as in 12 of 15 patients in Groups A and B, who could be followed up for more than three months, the lesions had spontaneously disappeared or left calcific residues. It is concluded that in Indian epileptic patients with SSECTL cysticercosis is the commonest aetiology. A treatment protocol for these patients is suggested on the basis of the findings.

Biopsy

Shunt surgery for hydrocephalus in tuberculous meningitis: a long-term follow-up study.

Hydrocephalus is a common complication of tuberculous meningitis. Case studies of 114 patients with tuberculous meningitis and hydrocephalus, who underwent shunt surgery between July, 1975, and June, 1986, were reviewed to evaluate the long-term outcome and to outline a management protocol for these patients based on the results. Seven factors were studied in each case: 1) age at admission; 2) grade on admission (I to IV, classified by the authors; Grade I being the best and Grade IV being the worst); 3) duration of alteration of sensorium; 4) cerebrospinal fluid (CSF) cell content at initial examination; 5) CSF protein levels at initial examination; 6) number of shunt revisions required; and 7) the necessity for bilateral shunts. During a long-term follow-up period ranging from 6 months to 13 years (mean 45.6 months), the mortality rate was 20% for patients in Grade I; 34.7% for patients in Grade II; 51.9% for patients in Grade III; and 100% for patients in Grade IV. Only the grade at the time of admission was found to be statistically significant in determining final outcome (p less than 0.001). Based on these results, the authors advocate early shunt surgery for Grade I and II patients. For patients in Grade III, surgery may be performed either if external ventricular drainage causes an improvement in sensorium or without selection. All patients in Grade IV should undergo external ventricular drainage and only those who show a significant change in their neurological status within 24 to 48 hours of drainage, should have shunt surgery.

Adolescent

Screening for hemoglobins S and C in newborn and adult blood with a monoclonal antibody in an ELISA procedure.

To facilitate the screening of blood for the presence of hemoglobins S or C, we devised an enzyme-linked immunoassay (ELISA). The ELISA procedure incorporated a murine monoclonal antibody (mAb), beta s-1, which recognized both Hb variants but did not react with Hb A, Hb A2 or Hb F. Hemoglobins in cord or adult hemolysates were coated on the surface of wells of polystyrene microtiter plates and treated with beta s-1 mAb, followed by goat anti-mouse IgG conjugated with horseradish peroxidase. After addition of tetramethylbenzidine substrate solution, a deep blue color developed, signifying the presence of Hb S or Hb C. The beta s-1 mAb ascites fluid could detect purified Hb S and Hb C when diluted to over 1/512,000 and cord blood hemolysates containing Hb/S or Hb C when diluted to 1/128,000. Although maximal reactivity was achieved using undiluted hemolysates, the ELISA system could easily detect Hb S and Hb C in cord blood hemolysates when diluted 10(-4). The sensitivity of the ELISA was 1%, which exceeds the lowest quantities of these variants normally found in cord blood. In addition, we found that the ELISA procedure was suitable for detecting Hb S/Hb C in whole blood as well. The entire assay could be conducted on multiple samples in less than 1 h, thus providing a specific, sensitive, rapid and simple screening technique for Hb S and Hb C in cord or adult blood.

Adult

The paradox of increased microvascular visualization with decreased perfusion in cerebral focal ischaemia in a primate model.

Microvasculature of the right caudate nucleus and insular cortex of monkeys with their right middle cerebral artery occluded was morphometrically measured with an image analysis system at 1/2, 4, 12, 24, and 48 hr and 2 weeks. A biphasic change in the microvasculature was observed. In the first phase up to 12 hr an increase in the number and length of the total microvasculature, visualized by alkaline phosphatase staining, along with a reduction in the number and length of the perfused part of the microvasculature, visualized by India ink perfusion, was observed. In the second phase after 48 hr, the number and length of the total microvascular bed as well as the perfused functional bed were significantly reduced.

Animals