Biomedical subjects

R Pahwa

Publications and source records attributed to R Pahwa.

At least 19 recordsLinked to original sources

PubMed1992

Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood.

Although hypercellularity is a common bone marrow finding in patients with human immunodeficiency virus type 1 (HIV-1) infection, the effect of HIV-1 on the hematopoietic system, which has been investigated in in vitro studies, is still controversial. In this study, we have investigated the effects of HIV-1 envelope glycoprotein, gp160, on the differentiation of hematopoietic progenitor cells derived from cord blood. Culture of cord blood mononuclear cells with gp160 resulted in enhancement of the in vitro growth of myeloid hematopoietic progenitors. To investigate the mechanism of the enhancement, adherent cells, T cells, or CD34-bearing hematopoietic progenitors were isolated and cultivated with gp160 in a variety of culture conditions. We have shown that gp160 had no direct effect on highly purified hematopoietic progenitors but exerted its enhancing effect indirectly via T cells, by induction of a humoral colony-stimulating factor(s). The activity of gp160 on T cells was abrogated by preincubation of gp160 with recombinant CD4 molecule and goat anti-gp120 antibody. These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis. Binding of gp160 with the cell surface CD4 molecule appears to be necessary for secretion of the colony-stimulating factor(s).

Antibodies↗

PubMed1992

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

The role of the CD4 molecule in activation of T-helper cells was examined by investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in conventional peptide antigen-specific cloned T-helper cells that are also reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are CD4+/CD45RO+/T-cell antigen receptor beta-chain variable region 12-positive and can respond to nominal peptide antigens and SEB by proliferation in the presence of class II major histocompatibility complex-expressing accessory cells. Although antigen and SEB were comparable in their ability to induce proliferative responses, interleukin 2 (IL-2) production, and IL-2 receptor alpha-chain expression, stimulation with SEB failed to trigger phosphatidylinositol hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a treatment inhibited antigen-induced proliferative responses of T cells with concomitant suppression of IL-2 production and IL-2 receptor expression. In contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate that the functional consequences of binding (ligation) of conventional antigen and of superantigen with the T-cell receptor are distinct in the context of both signal transduction pathways and participation of CD4 molecules.

Antibodies, Monoclonal↗

PubMed1992

The effect of acetazolamide on essential tremor: an open-label trial.

We studied the effect of the carbonic anhydrase inhibitor acetazolamide on 24 patients with essential tremor by patient self-evaluation of functional disability, rating of motor task function, and clinical rating of tremor severity. Acetazolamide significantly reduced tremor severity, but there was no statistically significant change in patient self-assessment of function or motor task rating. Although side effects were common, over half the patients elected to remain on the drug.

Acetazolamide↗

PubMed1992

Olfactory function in essential tremor.

Olfactory function, assessed by the University of Pennsylvania Smell Identification Test, was normal in essential tremor (ET) patients and significantly reduced in patients with Parkinson's disease (PD). This finding further supports a lack of association between ET and PD.

Female↗

PubMed1991

Forensic toxicology and insects: a minireview.

In cases of suspicious death, various postmortem changes and the insect species infesting the corpse have been employed to compute the time of death. Recently, chemical analysis of the life stages of insects infesting the corpse has revealed poisons and drugs consumed for suicide in the body of the deceased. This new area can provide proof of the cause of death. It is recommended that whether or not there is suitable tissue samples for the analysis, the developmental stages of insects thriving on the carcass should always be collected as exhibits for analysis.

Adult↗

PubMed1990

Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes.

The circulating T lymphocytes of a female child with recurrent opportunistic infections were normal in number and phenotype but exhibited poor proliferation and decreased synthesis of the T-cell growth factor interleukin (IL) 2 in response to mitogens. Recombinant IL-2 fully restored the proliferative responses of her T cells, suggesting that her poor immune function was related to IL-2 deficiency. Northern blot analysis of total cellular RNA from the patient's T cells revealed markedly decreased levels of IL-2 mRNA of normal size. In addition, mRNA levels of other lymphokines selectively expressed by T cells, which include IL-3, IL-4, and IL-5, were either severely depressed or absent. The levels of interferon gamma mRNA were moderately decreased, while those of granulocyte-macrophage colony stimulating factor, a lymphokine the production of which is not restricted to T cells, were unaffected. The decreased level of lymphokine mRNA in the patient's T lymphocytes was not from enhanced catabolism but resulted from a diminution in the transcription rate of the affected lymphokine genes. Normal transduction via the T-cell receptor/CD3 complex of biochemical signals necessary for the initiation of lymphokine gene transcription indicated that the defect was distal to the membrane signal-transducing apparatus. The defect is hypothesized to involve a T-cell-specific trans-acting regulatory factor required for transcription of the affected lymphokine genes.

Antibodies, Monoclonal↗

PubMed1990

Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA.

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.

Antigens, CD↗

PubMed1990

The toxicity of yellow oleander (Thevetia neriifolia juss) seed kernels to rats.

Toxic effects of yellow oleander (Thevetia neriifolia Juss) seed kernels were evaluated against the roof rat (Rattus rattus Linn). Crushed ground seed kernels were fed with bait at 20 and 30% concentrations. The bait was fed up to mortality or for a maximum of 10 d. Major signs of poisoning observed were hind limb paralysis, rolling of the body on the long axis, circular flailing of the tail, muscular twitch, tetanic convulsions, tremors, collapse and death. Significant reductions in the rats' weights were observed. The observed mortalities were 16/20 and 18/20 with the above respective doses. Statistically significant reductions in hemoglobin, red blood cell count, total leucocyte count and neutrophils, and increased lymphocytes were observed. Reductions in blood glucose and serum proteins, and increased lymphocytes were observed. Reductions in blood glucose and serum proteins, and increased BUN, SGOT and LDH, were also significant. Histopathological studies showed inflammatory and degenerative changes in the liver and kidney. Severe to moderate fatty metamorphosis, congestion, hepatocytolysis, nuclear degeneration, pyknosis, and necrosis were major changes in the liver. Proliferation of glomerular endothelium, hypercellularity of the glomerulus, necrosis of convoluted tubular epithelium, disappearance of nuclei and pyknosis were important changes in the kidney cortical region. Atrophy, erosion and inflammatory changes were observed in the stomach mucosal linings.

Animals↗

PubMed1989

Management of a novel immune deficiency with IL-2 therapy.

The present study describes a female child, who had a primary defect in the ability of her T-cells to secrete interleukin-2. Numbers of B- and T-cells were normal, but their functions were severely deficient. The patient had decreased immunoglobulins and poor ability to mount antibody responses. Phytohemagglutinin (PHA) and antigen-driven lymphoproliferative responses were diminished and were correctable in vitro with exogenous IL-2. Upon stimulation with PHA the patient's lymphocytes expressed IL-2 receptors normally, but were grossly deficient in endogenous IL-2 production. The patient was diagnosed as having a form of severe combined immunodeficiency disease at 6 months of age. Two attempts at immune reconstitution by haploidentical bone marrow transplantation failed to result in sustained engraftment. At age 18 months, treatment was initiated with rIL-2 10,000 units/kg i.v. daily and gradually increased to 30,000 units/kg. A marked improvement was noted, clinically as well as in T-cell immune functions. The child has been maintained on rIL-2 treatment at home for the past year without significant adverse effects, and she is currently receiving 30,000 units/kg of rIL-2 three times a week. This case illustrates that IL-2 is a potentially useful therapeutic modality which can be safely administered for prolonged periods to children with primary immunodeficiency diseases.

B-Lymphocytes↗

PubMed1989

Recombinant interleukin 2 therapy in severe combined immunodeficiency disease.

Severe combined immunodeficiency disease (SCID) is a congenital disorder of severe B- and T-lymphocyte dysfunction in which several pathogenic mechanisms have been identified. The present study describes a female child with SCID who had a primary defect in the ability of T cells to secrete interleukin 2 (IL-2). B- and T-cell numbers were normal, but their functions were severely deficient. Mitogen and antigen-driven lymphoproliferative responses were diminished but were correctable in vitro with recombinant IL-2 (rIL-2). The patient's phytohemagglutinin-stimulated lymphocytes expressed IL-2 receptors normally. Despite the presence of the gene for IL-2, the patient's cells were grossly deficient in messenger RNA for IL-2 and endogenous IL-2 production. Pokeweed mitogen-driven B-cell differentiation was decreased and was not corrected by the addition of normal T cells to the B cells. Two attempts at immune reconstitution by haploidentical bone marrow transplantation failed. Therapy with rIL-2 (30,000 units/kg, given daily i.v.) resulted in marked clinical improvement as well in improved T-cell functions. The child, now 3 yr old, has been on rIL-2 therapy for 2 yr and receives rIL-2 (30,000 units/kg) three times weekly at home. This case study points to a new direction in the treatment of such disorders with rIL-2.

B-Lymphocytes↗

PubMed1989

In vitro synthesis of human immunodeficiency virus-specific antibodies in peripheral blood lymphocytes of infants.

An assay system was developed for the analysis of antibodies secreted in vitro against human immunodeficiency virus (HIV) by cultured peripheral blood lymphocytes of HIV-infected individuals. Cultures of peripheral blood lymphocytes were established with medium alone or with medium containing Epstein-Barr virus (EBV) or pokeweed mitogen. HIV antibodies were determined by an ELISA performed with commercial kits in which a whole virus extract served as antigen. Optimal antibody secretion was detected in 7-day peripheral blood lymphocyte cultures to which EBV had been added to provide polyclonal B-cell activation. Pokeweed mitogen-induced antibody secretion and spontaneous antibody secretion were less consistent. With EBV as a stimulus, the sensitivity and specificity of this assay for determining HIV infection status were each 100% in adults. When the assay was applied to infants and children, 23 of 24 symptomatic HIV-seropositive children (class P-2) and 11 of 33 asymptomatic seropositive infants aged less than or equal to 15 months (class P-0) tested positive for EBV-induced antibody secretion. Six of the 11 P-0 patients who tested positive have progressed to develop symptomatic disease, while the remainder are still seropositive at ages 2-15 months. Of the infants who were negative in this assay, all have remained asymptomatic. Treatment with 3'-azido-3'-deoxythymidine in infected adults and children has resulted in transient suppression of the in vitro antibody response in some instances. Thus EBV-induced synthesis of HIV-specific antibodies in vitro is a sensitive and specific indicator of HIV infection and is of help in determining infection status of asymptomatic seropositive infants who are classified as having "indeterminate" infection.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Cerebral arteriovenous oxygen difference as an estimate of cerebral blood flow in comatose patients.

The hypothesis that cerebral arteriovenous difference of oxygen content (AVDO2) can be used to predict cerebral blood flow (CBF) was tested in patients who were comatose due to head injury, subarachnoid hemorrhage, or cerebrovascular disease. In 51 patients CBF was measured daily for 3 to 5 days, and in 49 patients CBF was measured every 8 hours for 5 to 10 days after injury. In the latter group of patients, when a low CBF (less than or equal to 0.2 ml/gm/min) or an increased level of cerebral lactate production (CMRL) (less than or equal to -0.06 mumol/gm/min) was encountered, therapy was instituted to increase CBF, and measurements of CBF, AVDO2, and arteriovenous difference of lactate content (AVDL) were repeated. When data from all patients were analyzed, including those with cerebral ischemia and those without, AVDO2 had only a modest correlation with CBF (r = -0.24 in 578 measurements, p less than 0.01). When patients with ischemia, indicated by an increased CMRL, were excluded from the analysis, CBF and AVDO2 had a much improved correlation (r = -0.74 in 313 measurements, p less than 0.01). Most patients with a very low CBF would have been misclassified as having a normal or increased CBF based on the AVDO2 alone. However, when measurements of AVDO2 were supplemented with AVDL, four distinct CBF patterns could be distinguished. Patients with an ischemia/infarction pattern typically had a lactate-oxygen index (LOI = -AVDL/AVDO2) of 0.08 or greater and a variable AVDO2. The three nonischemic CBF patterns had an LOI of less than 0.08, and could be classified according to the AVDO2. Patients with a normal CBF (mean 0.42 +/- 0.12 ml/gm/min) had an AVDO2 between 1.3 and 3.0 mumol/ml. A CBF pattern of hyperemia (mean 0.53 +/- 0.18 ml/gm/min) was characterized by an AVDO2 of less than 1.3 mumol/ml. A compensated hypoperfusion CBF pattern (mean 0.23 +/- 0.07 ml/gm/min) was identified by an AVDO2 of more than 3.0 mumol/min. These studies suggest that reliable estimates of CBF may be made from AVDO2 and AVDL measurements, which can be easily obtained in the intensive care unit.

Arteries↗

PubMed1989

Clinical experience with a continuous monitor of intracranial compliance.

Intracranial compliance, as estimated from a computerized frequency analysis of the intracranial pressure (ICP) waveform, was continuously monitored during the acute postinjury phase in 55 head-injured patients. In previous studies, the high-frequency centroid (HFC), which was defined as the power-weighted average frequency within the 4- to 15-Hz band of the ICP power density spectrum, was found to inversely correlate with the pressure-volume index (PVI). An HFC of 6.5 to 7.0 Hz was normal, while an increase in the HFC to 9.0 Hz coincided with a reduction in the PVI to 13 ml and indicated exhaustion of intracranial volume-buffering capacity. The mean HFC for individual patients in the present study ranged from 6.8 to 9.0 Hz, and the length of time that the HFC was greater than 9.0 Hz ranged from 0 to 104.8 hours. The mortality rate increased concomitantly with the mean HFC, from 7% when the mean HFC was less than 7.5 Hz to 46% when the mean HFC was 8.5 Hz or greater. The length of time that the HFC was 9.0 Hz or greater was also associated with an increased mortality rate, which ranged from 16% if the HFC was never above 9.0 Hz to 60% if the HFC was 9.0 Hz or greater for more than 12 hours. In 12 patients who developed uncontrollable intracranial hypertension or clinical signs of tentorial herniation during the monitoring period, 75% were observed to have had an increase in the HFC to 9.0 Hz or more 1 to 36 hours prior to the clinical decompensation. The more rapid the increase in the HFC, the more likely the deterioration was to be caused by an intracranial hematoma. Continuous monitoring of intracranial compliance by computerized analysis of the ICP waveform may provide an earlier warning of neurological decompensation than ICP per se and, unlike PVI, does not require volumetric manipulation of intracranial volume.

Adaptation, Physiological↗

PubMed1989

The toxicity of Mexican poppy (Argemone mexicana L) seeds to rats.

Toxicolethal effects of seeds of mexican poppy (Argemone mexicana L) were investigated in to roof rat, (Rattus rattus L). The argemone seeds were fed at 100% of the diet up to the death or for a maximum of 10 days. Observed signs of poisoning were sedation, passiveness, sluggishness, feeble or no muscular jerks, abdominal contractions and increased defecation. Also black secretions from the eyes, corneal opacity, erection of hairs, and edema of the hind legs and submandibular space in were noted. Fourteen of 16 rats died. Significant reduction in the weights of the rats was observed. There were significant increases in blood glucose, BUN and SGOT. Major histopathological lesions were: hepatocytolysis, nuclear degeneration, pyknosis, cloudy swelling and dilatated sinusoids disturbing the lobulalar architecture of the liver; proliferated endothelium of glomeruli, hemorrhage in glomeruli and interstitium, and cloudy swelling of convoluted tubular epithelium in the kidney cortical region; erosion and atrophy of the upper stomach mucosa and calcification in the cardiac stomach, and; erosion and congestion of the upper mucosa of the duodenum. No change was noticed in the ileum.

Animals↗

PubMed1988

Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS.

Acyclovir has become the treatment of choice for varicella-zoster virus (VZV) infections in immunocompromised individuals. This article describes a 4-year-old girl congenitally infected with human immunodeficiency virus who developed a continuous cutaneous infection with VZV that persisted over a 14-month period until her death. Initial episodes of varicella and zoster were responsive to acyclovir treatment; however, subsequent recurrences necessitated administration of multiple courses of acyclovir. Lesions became markedly hyperkeratotic, slow healing, and persistent despite acyclovir therapy. Numerous attempts to isolate virus from the lesions yielded only one isolate late in the course of therapy. This virus clearly demonstrated acyclovir resistance in vitro. Bizarre manifestations of VZV infection could present both diagnostic and therapeutic dilemmas. Prolonged acyclovir treatment of highly immunocompromised patients with acquired immunodeficiency syndrome and severe VZV may lead to the appearance of resistant virus.

Acquired Immunodeficiency Syndrome↗

PubMed1988

The toxicity of Indian Calotropis procera RBr latex in the black rat, Rattus rattus Linn.

Toxicity studies with latex of Calotropis procera RBr were conducted in the black rat, Rattus rattus. The latex was fed through bait prepared from wheat flour, ground nut oil and sugar at concentrations of 5, 7.5 or 10% (W/W). The bait was fed up to mortality and for a maximum of 10 days. The signs produced were passivity, sluggishness, sedation, dyspnea, weakness, reduction in weight, anorexia, diarhhea, hematuria, bleeding from nose, eyes and anus, eye lens opacity, mild tetanic convulsions, collapse and death. The observed mortalities were 56.25, 68.75 and 87.5% with the respective doses. Histopathological studies showed: cloudy swelling of hepatocytes, inflammatory changes, Kupffer cell hyperlasia, cytoplasmic granulation, hepatocytolysis, compactness of lobular architecture, and occasional hemorrhage in the liver; cloudy swelling of convoluted tubular epithelium, inflammatory changes and hemorrhage in the kidney; erosion, increased mucus secretion, congestion and infiltration of lymphocytes in portions of the alimentary canal.

Animals↗

PubMed1987

Prematurity, hypogammaglobulinemia, and neuropathology with human immunodeficiency virus (HIV) infection.

Infection with the human immunodeficiency virus (HIV) is characteristically associated with hypergammaglobulinemia in both adult and pediatric cases. We report herein four infants who had an HIV infection in association with severe hypogammaglobulinemia and did not exhibit antibodies against HIV. HIV was isolated antemortem or postmortem in all four infants from either peripheral blood, cerebrospinal fluid, or body tissues. HIV infection could be presumed to be acquired transplacentally in two infants and by way of infected blood transfusions during the neonatal period in the other two. Each infant became symptomatic within the first year of life and developed rapidly progressive manifestations of the disease. Features that were common to all four infants include premature birth, failure to thrive, hepatomegaly, and progressive neurological abnormalities that were associated with intracranial calcifications. We concluded that, when infection occurs early in development either by transplacental exposure to the virus or from blood transfusion in small premature infants, hypogammaglobulinemia and deficiency of antibody production leading to the absence of antibody responses on which diagnosis is usually based can occur. Furthermore, progressive central nervous system disease may be a frequent finding in such infants, and this may lead to cerebral calcifications that must be attributed to the HIV infection itself and not to complicating infections--e.g., toxoplasmosis. It is suggested that patients with hypogammaglobulinemia, antibody deficiency syndrome, and central nervous system disease have an extremely bad prognosis.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Identification of a second T-cell antigen receptor in human and mouse by an anti-peptide gamma-chain-specific monoclonal antibody.

We developed a monoclonal antibody (mAb) (9D7) against a synthetic peptide (P13K) selected from the deduced amino acid sequence of the constant region of the gamma chain of the murine T-cell antigen receptor (TCR) (amino acids 118-130). Using this mAb, we identified a putative second TCR expressed on peripheral blood lymphocytes from a patient with severe combined immunodeficiency (SCID) that were propagated in culture with recombinant interleukin 2 (rIL-2) and Con A. This mAb immunoprecipitated two polypeptide chains of 40 and 58 kDa under nonreducing conditions and of 40 and 56 kDa under reducing conditions from 125I-labeled denatured lysates of T3+ WT31- lymphocytes expanded in culture from a SCID patient. These polypeptide chains were not disulfide linked and were not present on human peripheral blood lymphocytes from normal donors cultured for 5 days with phytohemagglutinin or for 2 weeks with rIL-2 and polyclonal activators or on cells of the Jurkat lymphoblastoid human T-cell line. Chemical crosslinking of 125I-labeled cells followed by immunoprecipitation with anti-Leu-4 mAb under nonreducing or reducing conditions revealed that the 40- and 56-kDa polypeptide chains were associated with the T3 differentiation antigen. These results were confirmed by sequential immunoprecipitation with anti-Leu-4 mAb followed by 9D7 anti-P13K mAb. The 9D7 anti-P13K mAb immunoprecipitated two polypeptide chains of 43 and 64 kDa from denatured lysates of lymphocytes from a patient with severe common variable immunodeficiency (CVI) that were expanded in culture with rIL-2 and Con A. Thus, this second TCR may be composed of two polypeptide chains (gamma gamma'), both of which appear to be the product of the gamma-chain gene. These experiments were done with polyclonal cell populations. Cloned T3+ WT31- cell populations are required to determine whether this TCR contains two gamma polypeptide chains. In contrast, only one polypeptide chain of 56 kDa was immunoprecipitated by the 9D7 anti-P13K mAb from peripheral blood lymphocytes from a patient with mild CVI expanded in culture with rIL-2 and polyclonal activators. Using the same 9D7 anti-P13K mAb and immunoblotting analysis, we identified a 35 kDa gamma-chain polypeptide under reducing conditions expressed on purified L3T4- Lyt2- BALB/c mouse thymocytes. This gamma-chain TCR is disulfide linked and has a molecular mass of 80 kDa under nonreducing conditions.

Amino Acid Sequence↗