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Biomedical subjects

A Guha

Publications and source records attributed to A Guha.

At least 109 records · Page 6Linked to original sources
PubMed1991

Inhibition of major histocompatibility complex class I antigen shedding up-regulates the surface expression of class I antigens on the lymphocyte cell surface.

Interferon-gamma induces the expression of major histocompatibility complex class I and class II gene products. Moreover, the density of MHC antigens present on the lymphocyte surface is regulated by exfoliation of the plasma membrane. To probe the cellular mechanisms involved in IFN-gamma-induced alteration of MHC antigen expression, we measured the effects of IFN-gamma on the rate of MHC antigen shedding and the biosynthesis of H-2Dd. Balb/c splenic lymphocytes were surface-iodinated with 125I and incubated in the presence and absence of up to 1000 U/ml IFN-gamma, or they were metabolically labeled with [35S]methionine with or without 500 U/ml IFN-gamma. Radioiodinated or 35S-labeled H-2Dd was quantified by immunoprecipitation of H-2Dd from detergent lysates of radiolabeled cells that were incubated with the appropriate antibody for 4-20 h at 37 degrees C. Monoclonal antibody 34-5-8 was employed as a specific probe for H-2Dd. Loss of radioiodinated H-2Dd from the cell surface was diminished by 75-90% at 12 h in tests of lymphocytes continuously cultured with IFN-gamma (compared to control, p less than 0.05). In contrast, the biosynthetic rate was unaffected during the initial 10 h of incubation. The net result of these changes was the early appearance of an increase in H-2Dd on the cell surface. This result was in accordance with data obtained by phenotyping the untreated and treated cells using double-antibody staining methods and fluorescence-activated cell sorter analysis. Our results suggest that IFN-gamma induces MHC expression by initially retarding the exfoliation of MHC antigens from the lymphocyte surface. Delayed effects on MHC expression may be, on the other hand, mediated by increased antigen biosynthesis.

Animals↗
PubMed1990

Experience with Ommaya reservoir in 120 consecutive patients with meningeal malignancy.

The Ommaya Reservoir plays an important role in a select group of neuro-oncology patients with meningeal malignancy. The benefits derived must be balanced against potential complications associated with insertion and use of the apparatus. Side effects may be minimized by careful attention to patient selection, pre-operative CAT scan (or MRI), precise surgical technique, perioperative prophylactic antibiotics and meticulous procedure during use of the reservoir.

Adolescent↗
PubMed1990

Hemophilia as a defect of the tissue factor pathway of blood coagulation: effect of factors VIII and IX on factor X activation in a continuous-flow reactor.

The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a shear rate of 57, 300, or 1130 sec-1. Factor Xa in the effluent was determined by chromogenic assay. The flux of factor Xa (moles formed per unit surface area per unit time) was strongly dependent on wall shear rate, increasing about 3-fold as wall shear rate increased from 57 to 1130 sec-1. The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2- to 3-fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor; however, when factors VIII and IX were present at their approximate plasma concentrations, factor Xa production rates were enhanced 15- to 20-fold. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia.

Blood Coagulation↗
PubMed1989

Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma.

T cell-mediated immune response against autologous melanoma cells was analyzed, at population and clonal levels, in 31 patients with recurrent and/or metastatic disease. Fresh PBL and lymph node lymphocytes (LNL) from melanoma-involved nodes were not cytotoxic against the respective melanoma cells. When activated in in vitro coculture (IVC) against the autologous melanoma cells in the presence of IL-2, a majority of the activated PBL and LNL became cytotoxic against the autologous targets. The activated effector cells were cloned in limiting dilution microcultures, and growing clones were phenotypically defined and were functionally characterized for cytotoxicity and for potential regulatory function. Functional T cell clones were obtained from 15 of 31 cases. Of these, CTL responses exhibiting cytotoxicity restricted against the autologous melanoma were seen in four cases. All four CTL clones were CD3+, CD8+, and CD4-. Three of these four CTL clones were studied extensively. All three of these CTL clones expressed MHC class I-restricted cytotoxicity. mAb anti-CD3 blocked cytotoxicity in two and enhanced cytotoxicity in the other. Neither autologous sera nor autologous nonactivated fresh PBL modulated the cytotoxic functions of the CTL clones at the effector phase. T cell lines exhibiting regulatory function were obtained in 11 cases. The regulatory T cell lines were CD3+, CD4+, and CD8-. In three cases CD4+ clones amplified the cytotoxic response in the PBL in coculture, while in eight other cases the T cell lines downregulated the cytotoxic responses. Such T cell-mediated down-regulations were either restricted to the autologous system, induced by D/DR antigens expressed by the autologous or allogeneic melanoma cells, or induced by stimulus other than D/DR antigens. Taken together, these findings clearly demonstrate the existence of T cell-mediated cytotoxic and regulatory responses against human melanoma.

Antigens, Neoplasm↗
PubMed1989

Improvement in post-traumatic spinal cord blood flow with a combination of a calcium channel blocker and a vasopressor.

We have recently shown that nimodipine, a calcium channel blocker, can increase spinal cord blood flow (SCBF) in normal rats and can improve SCBF after spinal cord trauma if the mean systemic arterial pressure (mSAP) is restored to normal levels by the vasopressor, adrenalin. The present study is a further analysis of the improvement in post-traumatic SCBF (measured with the hydrogen clearance technique) with the combination of adrenalin and nimodipine. In addition, image analysis was used to study the potential risk of this combination for exacerbating intramedullary hemorrhage in the injured spinal cord. SCBF, mSAP, and other physiologic parameters were measured preinjury, postinjury, and post-treatment. A 53.0-gram clip compression injury at the T1 spinal segment was delivered for 1 minute to three treatment groups (saline, adrenalin, and adrenalin plus nimodipine) comprised of five rats each. Injury caused a marked decline in SCBF and mSAP. Treatment with adrenalin alone or combined with nimodipine (1.5 micrograms/kg/min IV) improved mSAP to 100-125 mm Hg. However, adrenalin alone failed to improve SCBF, whereas nimodipine plus adrenalin produced a marked improvement of approximately 60% in post-traumatic SCBF. Morphometric analysis showed no significant difference between per cent area or volume of hemorrhage between the three treatment groups, although there was a trend for increased hemorrhage in the adrenalin-alone group perhaps due to the higher post-traumatic mSAP in this group. Further studies are required to find the minimal elevation in mSAP produced by a vasopressor that would still cause an improvement in post-traumatic SCBF by nimodipine, and to determine whether this combination improves function after spinal cord injury.

Animals↗
PubMed1989

Vertex epidural hematomas.

Four cases of vertex epidural hematomas are presented to illustrate the unique management problems which set them apart from their more common counterparts located over the temporal convexity. Diagnosis requires a high degree of suspicion as vertex epidural hematomas are often missed by conventional horizontal scanning. Coronal computed tomographic scanning should be undertaken in all suspected cases. Clinical symptoms exceeding the small volume of clot may be present due to venous obstruction and disruption of cerebrospinal fluid absorption. Evacuation of the clot usually leads to clinical improvement.

Adult↗
PubMed1989

Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats.

We looked at the relation between systemic arterial blood pressure and recovery from spinal cord injury by inducing both hypertension and hypotension in 25 rats randomly allocated to five equal groups. The rats received no injury, a mild (2.3-g), or a severe (53.0-g) spinal cord injury lasting 1 minute. We used the hydrogen clearance technique to measure spinal cord blood flow at the injury site (T1) and at an adjacent site (C6). Mean systemic arterial blood pressure was either increased with adrenaline or decreased by phlebotomy in 20-mm-Hg intervals except for the severe-injury group, in which the posttraumatic pressure could only be increased with adrenaline. Spinal cord blood flow remained constant in the no-injury group between 81 and 180 mm Hg. After a mild injury, induced moderate hypertension (121-140 mm Hg) improved spinal cord blood flow significantly, whereas hypotension decreased it in a linear fashion. Severe injury caused a marked decrease in spinal cord blood flow and mean systemic arterial blood pressure. Even extreme hypertension (161-180 mm Hg) induced by adrenaline did not significantly increase spinal cord blood flow at T1 but caused hyperemia at C6 due to loss of autoregulation. In conclusion, normotension should be attempted, irrespective of the severity of spinal cord injury. Induced hypertension after severe spinal cord injury was not beneficial in improving spinal cord blood flow at the injury site while potentially increasing hemorrhage and edema.

Animals↗
PubMed1989

Subependymoma of the thoracolumbar cord. Case report.

Subependymomas are benign, usually asymptomatic, intraventricular tumors, the origin of which remains controversial. Spinal cord subependymomas are rare: a literature review yields 10 previous cases which are critically appraised in this report. A case of thoracolumbar intramedullary subependymoma is reported, and the histology, ultrastructure, and pre- and postoperative management are reviewed. Awareness that subependymomas may occur as a separate entity in the spinal cord should lead to increased frequency of diagnosis and a better understanding of the biological behavior of these tumors.

Adult↗
PubMed1988

Synthesis of prostaglandin E by peritoneal macrophages from NZB/W mice.

Peritoneal macrophages from NZB/W (murine lupus) mice spontaneously produce less prostaglandin E (PGE) than peritoneal macrophages from immunologically normal mice. Reduced PGE synthesis is seen as early as 2 months of age and becomes more profound as disease progresses. It is suggested that impaired production of PGE by peritoneal macrophages from NZB/W mice may account in part for abnormal macrophage function observed in these animals.

Age Factors↗
PubMed1988

Acute cardiovascular effects of experimental spinal cord injury.

The effects of acute head injury or subarachnoid hemorrhage on the cardiovascular system (CVS) are well known, but data are lacking on the effects of acute spinal cord injury (SCI) on the CVS. The clip compression SCI rat model was used to measure changes in the mean systemic arterial pressure (mSAP), cardiac output (CO), heart rate (HR), total peripheral resistance (TPR), and central venous pressure (CVP) after SCI. Three groups of five animals each were anesthetized with chloralose-urethane: one group underwent only the surgical procedures including laminectomy, and the other two received either a 2.3- or 53.0-gm injury at the T1 spinal cord segment for 1 minute. The CO was measured using the thermodilution technique. CVS parameters were measured before injury, and then at designated times for 135 minutes after SCI. Analysis of variance and paired t-test with significance at p = 0.05 were used for analysis. There were no CVS changes as a result of anesthesia, operative time, or laminectomy alone. Cardiovascular system (CVS) changes occurred after the 2.3- and 53.0-gm. injuries but were significantly different only in the 53.0-gm injured animals. In this group mSAP increased from a preinjury value of 105 +/- 8 mm Hg to 178 +/- 11 mm Hg as a result of SCI, followed by a prolonged period of hypotension (46 +/- 15 mm Hg) lasting until 135 min post SCI. The CO after SCI also decreased from 394 +/- 22 to 218 +/- 29 ml/min/kg with the TPR reaching a minimal level at 45 min post SCI (265 +/- 23 to 213 +/- 29 mm Hg/ml/min gm wt), after which it returned to preinjury values. There were no significant changes in the CVP in either group. In the 53.0-gm group significant bradycardia (492 +/- 7 to 356 +/- 44 beats/min) was observed by 45 min and continued to decrease until 135 min after SCI. Thus the CVS showed two major alterations after severe SCI: post-traumatic hypotension, and a parallel decline in CO. There were no major changes in TPR, HR, or CVP, although HR ultimately declined. These findings suggest that the decline in CO was not entirely due to decreased sympathetic tone, but may also have resulted from direct myocardial injury, similar to that demonstrated after head injury or subarachnoid hemorrhage.

Animals↗
PubMed1988

Solitary condylomatous papilloma of the bronchus.

Two case reports of solitary bronchial papillomas are presented. The histologic features of the lesions are those of squamous papillomas exhibiting prominent condylomatous changes. Immunoperoxidase stains revealed the presence of human papillomavirus antigens in the koilocytotic cells. Ultrastructural studies demonstrated possible intranuclear viral-size particles. Solitary condylomatous papillomas of the bronchus should be distinguished from solitary bronchial squamous papillomas that do not have condylomatous features. The rationale for this separation is the likelihood of a viral origin for these condylomatous papillomas and their potential for malignant change.

Aged↗
PubMed1987

Assessment of spinal cord injury by counting corticospinal and rubrospinal neurons.

This paper describes an objective, quantifiable technique for assaying the degree of severity of spinal cord injury. Twenty-one rats underwent a C7-T1 laminectomy: 12 received a C8 spinal cord clip compression injury with forces of either 2.3, 16.9 or 53.0 g; 4 had cord transection at C8, and 5 had no cord lesion. Postoperative clinical neurological assessment was performed by the inclined plane method. At 4 weeks, the spinal cord-injured rats underwent a T10 transection and insertion of a Gelfoam pledget impregnated with horseradish peroxidase (HRP). HRP was similarly administered to 9 normal rats. Longitudinal sections of the spinal cord encompassing the injury site were stained with Luxol fast blue, and coronal sections from the cerebrum and midbrain were processed for HRP reactivity with tetramethylbenzidine. Labelled corticospinal and rubrospinal neurons were counted in every 6th section to derive a cortical score (CS) and a red nucleus score (RNS) for each animal. The CS reflected the extent of the pathological changes at the site of cord injury and the ln CS decreased linearly with increasing injury severity (P less than 0.0001). In contrast, the RNS was only reduced in animals with severe (53.0 g) cord injuries (P less than 0.0006). The degree of preservation of the dorsal columns including the corticospinal tracts at the injury site correlated with the CS, whereas the RNS was related to the degree of preservation of the lateral columns. Counts of rubrospinal neurons, but not corticospinal neurons, correlated closely (r = 0.96, P less than 0.001) with the inclined plane results, suggesting the importance of non-pyramidal tracts in controlling gross motor function. Thus, counting corticospinal and rubrospinal neurons is an objective, reliable test of the severity of experimental spinal cord injury.

Animals↗
PubMed1987

Cell-mediated amplification and down regulation of cytotoxic immune response against autologous human cancer.

The cytotoxic host immune response toward autologous human cancer may be regulated by the immunoregulatory network. Here we show that helper T cells, cloned from peripheral blood lymphocytes that were sensitized in vitro against an autologous human malignant paraganglioma, proliferated against and made interleukin 2 when cocultured with the tumor-associated antigen in the presence of autologous accessory cells. Furthermore, the helper cell clones amplified cytotoxic immune response by peripheral blood lymphocytes against the paraganglioma cells in coculture with the blood lymphocytes and the paraganglioma cells. An autologous T cell line bearing suppressor phenotype, established from a lymph node that had been infiltrated with the paraganglioma tumor cells, in contrast to the helper cells, selectively suppressed the cytotoxic immune response by the blood lymphocytes against the paraganglioma cells in identical coculture. These results, therefore, demonstrate the existence of cell-mediated immunologic regulations of the cytotoxic immune response (concurrent amplification and suppression in the same host) against an autologous human tumor.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Activation of autoreactive cytolytic T lymphocyte clone against human melanoma by anti-T3 monoclonal antibody and autologous accessory cells.

A cytotoxic T-lymphocyte (CTL) clone Tc1.8 was derived in a limiting dilution culture from a single cell that was derived from melanoma-involved lymph node lymphocytes activated in in vitro coculture against the autologous melanoma cells (VIP). The clone Tc1.8 (T3+, T8+, T4-, and Leu7-) expressed restricted cytolytic activity against only the autologous target VIP. As it aged in continuous culture containing interleukin 2, Tc1.8 lost cytolytic activity. The cytolytic function could be restored, however, with monoclonal antibody (MoAb) against T3 (OKT3) or with F(ab')2 fractions of OKT3, and upon restimulation with irradiated accessory cells. OKT3-mediated reinduction of cytotoxicity by the aged Tc1.8 could not be achieved if the T3 molecules were modulated from the effector cell surface following overnight incubation of Tc1.8 with saturating concentrations of OKT3 MoAb. Following reactivation with OKT3 Tc1.8 gained cytolytic function against NK targets in addition to VIP. Reactivation with F(ab')2 fractions of OKT3 and with autologous accessory cells, however, maintained its restricted antigen fidelity. The NK-like activity of Tc1.8 upon reactivation with OKT3 resulted from conjugate formation between the activated Tc1.8 and NK targets via the activating ligand itself. Thus, upon stimulation with anti-T3 MoAb and with autologous accessory cells, independently, the autoreactivity could be restored in an aged and inactive CTL clone.

Antibodies, Monoclonal↗