PubMed Health⌕ Search

Biomedical subjects

N S Khan

Publications and source records attributed to N S Khan.

At least 19 recordsLinked to original sources
PubMed2006

Roles for the interleukin-4 receptor and associated JAK/STAT proteins in human articular chondrocyte mechanotransduction.

OBJECTIVE: To identify functional interleukin-4 (IL4) receptor (IL4R) subtypes and associated Janus kinase/signal transducers and activators of transcription (JAK/STAT) molecules in human articular chondrocytes and assess the role of JAK/STAT proteins in chondrocyte mechanotransduction. METHODS: Expression of IL4R subunits and associated molecules was assessed by immunohistochemistry and western blotting. Functional IL4R were identified by chemical crosslinking of IL4-stimulated chondrocytes and western blotting. JAK and STAT phosphorylation was assessed by western blotting. RESULTS: Chondrocytes from normal and osteoarthritic (OA) cartilage express IL4Ralpha, gammac and IL13Ralpha1 subunits (components of the Type I and Type II IL4R). In the presence of IL4 only functional Type II IL4Rs were identified in normal or OA chondrocytes. With the exception of STAT2, no differences in JAK/STAT expression were detected between normal and OA cartilage. STAT2 was expressed in OA but not normal chondrocytes. Mechanical stimulation (MS) resulted in an IL4R-dependent increase in phosphorylated Tyk2 in normal chondrocytes, which could be abolished by IL1beta preincubation. No phosphorylation of STAT5 or STAT6 was detected in either normal or OA chondrocytes following mechanical stimulation (MS) IL4 stimulation resulted in a decrease in Tyk2 phosphorylation and an increase in phosphorylation of STAT6 in both normal and OA chondrocytes. CONCLUSION: Chondrocytes from normal and OA cartilage signal through a Type II IL4R. This signalling is via a STAT6-independent pathway. Differences in IL4 signalling are likely due to crosstalk between integrin and cytokine signalling pathways, and not differences in IL4R expression.

Cartilage, Articular↗
PubMed2005

Role of nucleic acid testing in cadaver organ donor screening: detection of hepatitis C virus RNA in seropositive and seronegative donors.

Hepatitis C virus (HCV) transmission by both seropositive and seronegative cadaver organ donors has been documented, yet nucleic acid testing is not routinely used to identify active infection in these donors prior to transplantation. Between November 2001 and February 2004, we screened 1445 cadaver organ donors for anti-HCV antibodies with either HCV EIA-2.0 (Abbott Diagnostics, Chicago, IL, USA) and/or Ortho HCV Version 3.0 ELISA (Ortho-Clinical Diagnostics, Raritan, NJ, USA) and confirmed seropositive samples with Chiron RIBA3.0 SIA (Chiron Corporation, Emeryville, CA, USA). Samples with sufficient volume (n = 726) were tested by the VERSANT HCV [transcription-mediated amplification (TMA)] Qualitative assay (Bayer Healthcare LLC, Tarrytown, NY, USA) which can be performed in approximately 5 h. Those with detectable HCV RNA and sufficient volume were quantified by the VERSANT HCV 3.0 (bDNA) Assay (Bayer Healthcare LLC) and/or the HCV RNA TMA Quantitative Assay (n = 23) and genotyped (n = 57). Seventy-seven of 1445 (5.3%) donors were seropositive, reactive by either one or both anti-HCV assays. Fifty-two of 63 (82.5%) of the seropositive samples had detectable HCV RNA and were genotyped. Seventeen of these samples had quantifications ranging from 128,123 to >7,692,307 IU/mL. Six of 663 (0.9%) seronegative samples had detectable HCV RNA. Their quantifications ranged from <9.3 to 1,464,799 IU/mL, and five of these six were successfully genotyped. As HCV RNA was demonstrated in samples from both our seropositive and seronegative cadaver organ donors, we are now incorporating nucleic acid testing into our donor screening/diagnostic algorithm.

Algorithms↗
PubMed2001

The natural substrate for nitric oxide synthase activity.

There has been little evidence to indicate that arginine is the natural substrate for generating nitric oxide synthase (NOS) activity. It is now shown that carnosine, which is widely distributed in tissues, is likely to be the true substrate. In tissue sections it gives a stronger NOS reaction than does arginine.

Animals↗
PubMed2000

Anti-oxidant, pro-oxidant properties of tannic acid and its binding to DNA.

Tannic acid has numerous food and pharmacological applications. It is an additive in medicinal products, and is used as a flavouring agent and as an anti-oxidant in various foods and beverages. We have previously shown that tannic acid in the presence of Cu(II) causes DNA degradation through generation of reactive oxygen species. On the other hand, it exhibits antimutagenic and anticarcinogenic activities, and induces apoptosis in animal cells. It is known that most plant-derived polyphenolic anti-oxidants also act as pro-oxidants under certain conditions. In this paper, we compare the anti-oxidant and pro-oxidant properties of tannic acid and its structural component gallic acid. It is shown that tannic acid is the most efficient generator of the hydroxyl radical in the presence of Cu(II), as compared with gallic acid and its analogues syringic acid and pyrogallol. The anti-oxidant activity of tannic acid was studied by its effect on hydroxyl radical and singlet oxygen mediated cleavage of plasmid DNA. Again, tannic acid provided the maximum protection against cleavage, while gallic acid and its structural analogues were found to be non-inhibitory or partially inhibitory. The results suggest that the structural features of tannic acid that are important for its anti-oxidant action are also those that contribute to the generation of hydroxyl radicals in the presence of Cu(II). Restriction analysis of treated phage DNA and thermal melting profiles of calf thymus DNA indicated that tannic acid strongly binds to DNA. Indirect evidence indicates that modification of DNA bases may also occur.

Animals↗
PubMed2000

Intimate examinations: use of chaperones in community-based family planning clinics.

We examined women's preferences regarding the use of chaperones during intimate examinations by a female doctor or nurse in community-based family planning clinics. An anonymous questionnaire was completed before consultation and examination by 126 women attending five family planning clinics selected to cover a range of social and ethnic groups. The questionnaire explored women's views regarding intimate examinations by a woman and the presence of a chaperone. A clear majority (107 vs 19) of our community clinic users preferred to be alone with the woman doctor or nurse during an internal examination. There was no significant difference in preference or strength of feeling when analysed by age, ethnicity or previous experience.

Adult↗
PubMed1998

Predominant expression of T helper 2 cytokines and altered expression of T helper 1 cytokines in long-term allograft survival induced by intrathymic immune modulation with donor class I major histocompatibility complex peptides.

BACKGROUND: We have recently demonstrated that three synthetic peptides corresponding to the alpha-helices of the alpha1 and alpha2 domains of the donor class I RT1.Aa molecule served as efficient CD4+ T-cell epitopes for indirect recognition of this molecule during cardiac allograft rejection in the PVG.R8-toPVG.1U rat strain combination. These peptides induce long-term graft survival when injected into the thymus 7 days before transplantation under the cover of transient immunosuppression with anti-rat lymphocyte serum. In this study, we analyzed intragraft cytokine gene expression to test whether immune deviation to the T helper (Th) 2 response is associated with long-term allograft survival in this model. METHODS: Intragraft cytokine gene expression was analyzed using a competitive reverse transcription polymerase chain reaction method we developed for this study. Cytokine gene expression was quantified in control allografts (n=5) with acute rejection and allografts from intrathymically manipulated recipients with acute rejection (n=5), delayed rejection (n=7), or no rejection (n=8). RESULTS: Long-surviving allografts expressed high levels of interleukin (IL)-4, IL-10, transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and undetectable levels of IL-2. Allografts that were rejected in a delayed fashion expressed mostly IL-2, IFN-gamma, and TGF-beta with low or undetectable levels of IL-4 and IL-10. Acutely rejected allografts from unmanipulated controls or peptide-manipulated recipients expressed high levels of IL-2, IFN-gamma, TGF-beta and undetectable levels of IL-4 or IL-10. All allografts also expressed T-cell receptor Cbeta gene, providing evidence for the presence of T-cell infiltrates in the grafts. CONCLUSIONS: These observations demonstrate that acute graft rejection in this model is associated with the expression of Th1 cytokines, IL-2, and IFN-gamma, whereas long-term survival is associated with predominant expression of Th2 cytokines, IL-4, and IL-10. The expression of IFN-gamma in long-surviving allografts in the absence of IL-2 provides evidence for altered activation of the Th1 response in this intrathymic immune modulation model.

Animals↗
PubMed1998

Increased arachidonic acid induced platelet chemiluminescence indicates cyclooxygenase overactivity in schizophrenic subjects.

Platelets were found to emit a burst of chemiluminescence during incubation with arachidonic or linoleic acid. This chemiluminescence response may indicate activation of the enzyme prostaglandin synthase in the arachidonate-induced platelet chemiluminescence as it is inhibited by aspirin. Stimulation of platelets with arachidonic acid and linoleic acid induced a concentration dependent chemiluminescence response. Platelets from drug naive schizophrenic subjects showed significantly increased arachidonic acid metabolism compared to control subjects. No significant difference was observed between schizophrenic and control subjects in the chemiluminescence response to linoleic acid. In schizophrenic subjects treated with neuroleptic drugs the overactive arachidonic acid response was normalized. Linoleic acid chemiluminescence response was unaffected by neuroleptic treatment. Hyperactive cyclooxygenase activity may reflect a similar condition in the brain and implicates prostaglandin pathway abnormalities in the pathogenesis of schizophrenia.

Adult↗
PubMed1998

Structural features of tannic acid important for DNA degradation in the presence of Cu(II).

Tannic acid has numerous food and pharmacological applications. It is an additive in medicinal products and is used as a flavouring agent and as an antioxidant in various foods and beverages. However, there are reports of its mutagenicity and carcinogenicity in bacterial and animal test systems. Tannic acid and its structural monomer gallic acid are also capable of inducing apoptosis in animal cells. We have earlier shown that tannic acid in the presence of Cu(II) causes DNA degradation through generation of reactive oxygen species such as hydroxyl radicals. In order to understand the chemical basis of the various biological properties of tannic acid we have studied the structure-activity relationship between tannic acid and gallic acid using the DNA cleavage assay. Results in the present paper indicate that gallic acid is considerably more active than tannic acid. However, if two of the three hydroxyl groups of gallic acid are methylated (syringic acid) the DNA degrading capacity declines sharply. Further, decarboxylation of gallic acid (pyrogallol) leads to enhancement of its activity. In conclusion, the results indicate that the DNA cleavage activity of tannic acid is due to its digalloyl moeity and that free hydroxyl groups are essential for cleavage.

Animals↗
PubMed1997

Hypothalamic hypertensive factor: an inhibitor of nitric oxide synthase activity.

Human and rat plasma and rat hypothalamus contain a cytochemically detectable substance, the concentration of which rises with an increase in salt intake. The plasma concentration of this material is also raised in essential hypertension and in the spontaneously hypertensive rat (SHR), the Milan hypertensive rat, and the reduced renal mass (RRM) hypertensive rat. In the normal rat, the greatest concentration is found in the hypothalamus of the SHR and the RRM hypertensive rat. The physicochemical characteristics of this cytochemically detectable hypothalamic hypertensive factor (HHF), including chromatographic behavior and molecular weight range, suggest that it may share features common to a substituted guanidine that is present in established nitric oxide synthase (NOS) inhibitors. It was therefore decided to determine the effect on NOS activity of the HHF obtained from mature SHR. The ability of HHF to inhibit NOS activity was studied on (1) NOS extracted from bovine aorta, rat brain, and human platelets by measuring the conversion of radiolabeled L-arginine to L-citrulline and (2) rat liver NOS measured indirectly with a cytochemical technique based on the stimulation of soluble guanylate cyclase activity in hepatocytes by NO. HHF showed a biphasic inhibitory action on platelet NOS activity that was greater with HHF obtained from SHR than from Wistar-Kyoto rats. HHF also had a biphasic inhibitory effect on hepatocyte NOS activity that was more potent when obtained from SHR. It is proposed that the increase in HHF, a novel form of NOS inhibitor that is elevated in SHR, may be involved in the rise in arterial pressure.

Animals↗
PubMed1996

Elevated endogenous nitric oxide synthase inhibitor in schizophrenic plasma may reflect abnormalities in brain nitric oxide production.

Cellular origins of methylarginines are not precisely known but the presence of free methyl and dimethylarginines in the brain were reported. We have investigated the circulating concentrations of asymmetrical dimethylarginine NG,NG-dimethylarginine (ADMA), NG,NG-dimethylarginine (SDMA), nitrate and nitrite levels in drug naive first episode schizophrenic patients and matched control subjects. Three of those patients were treated with neurolepties for 3 months. Plasma ADMA levels increased significantly but nitrate levels were significantly low compared to control subjects. Drug treatment apparently lowered ADMA levels and increased nitrate levels in plasma. Methylation of arginine to methylarginines may have an important role in regulating signal transduction through the nitric oxide system in the brain, and suggest novel therapeutic targets.

Adult↗
PubMed1996

Pediatric emergency physician interpretation of plain radiographs: Is routine review by a radiologist necessary and cost-effective?

STUDY OBJECTIVE: To determine the concordance rate of plain radiograph interpretations by pediatric emergency physicians and pediatric radiologists, to evaluate the effect of incorrect radiologic diagnosis on patient management, and to evaluate the necessity and cost-effectiveness of routine follow-up review of all plain radiographs by a radiologist. METHODS: We assembled a prospective series of all patients who presented to the emergency department of an urban tertiary care children's hospital and underwent plain radiography between October 1 and October 31, 1994. Pediatric emergency physicians documented their interpretations. Within 24 hours, films were reviewed by a pediatric radiologist. The two interpretations were classified as concordant or discordant and were further assessed for medical significance and subsequent change in management. RESULTS: During the study period, 707 radiographic examinations were performed: chest, 56%; skeletal excluding spine, 20.1%; abdomen, 11.9%; sinus, 4.2%; spine, 3.6%; and other, 4%. The accuracy or concordance rate was 90.2% (638 of 707) for pediatric emergency physician interpretations; clinical management was unchanged in 96.9% (685 of 707) of the cases. Of the 69 discordant interpretations, 48 were clinically significant, with 22 requiring changes in management. They included 9 false-negative interpretations by pediatric emergency physicians: (5 fractures, 2 cases of pneumonia, 1 case of sinusitis, 1 case of cardiomegaly); 10 false-positive interpretations by pediatric emergency physicians (5 fractures, 4 cases of pneumonia, 1 case of sinusitis), and 3 false-positive interpretations by radiologists (1 case of C-2 spine subluxation, 1 retropharyngeal abscess, and 1 case of necrotizing enterocolitis). No adverse outcomes resulted from these misinterpretations. Routine review of all plain radiographs by a radiologist represents an estimated $210,000 annual cost to the patients and payers. CONCLUSION: Radiograph interpretations by pediatric emergency physicians were generally accurate, and no adverse outcomes occurred as a result of misinterpretation. Clinical assessment probably assisted these physicians in interpreting the radiographs of high-risk patients. Judicious consultation with a radiologist during the initial presentation of a high-risk patient, when deemed warranted by the pediatric emergency physician, will help the emergency physician deliver high-quality, cost-effective health care. Given the overall clinical accuracy rate of radiograph interpretations by the pediatric emergency physicians and the cost of routine review of all plain radiographs in the ED by a radiologist, routine review versus selective specialty consultation must be further evaluated.

Child↗
PubMed1995

Elevated platelet calcium mobilization and nitric oxide synthase activity may reflect abnormalities in schizophrenic brain.

Schizophrenia has a diverse nature of clinical symptoms and a number of hypotheses have been suggested to explain its aetiological basis. In this study we have examined two aspects of membrane function, receptor-activated calcium mobilization and calcium activated nitric oxide synthase activity in schizophrenic subjects. Thrombin induces mobilization of calcium ions from intracellular stores. The platelet response of drug naive schizophrenics was found to be significantly increased over a range of thrombin concentrations (0.01 to 0.60 U/ml) compared to control subjects. Possible involvement of nitric oxide (NO) in the aetiology of schizophrenia was investigated. NO has been functionally linked to both dopaminergic and glutamatergic systems both of which are strongly implicated in the biochemical pathology of schizophrenia. Nitric oxide synthase (NOS) activity was determined in platelets of controls, schizophrenic and panic disorder subjects. Enzyme activity was found to be significantly higher in platelets of drug naive schizophrenic subjects compared to controls, drug treated schizophrenics and panic disorder subjects. It is suggested that there is an imbalance of the calcium-induced L-arginine- nitric oxide pathway in platelets of schizophrenic subjects which may be modified by neuroleptic treatment. This imbalance may be mirrored in the central nervous system in particular at the NMDA receptor. It is possible that such a disturbance in the L-arginine-nitric oxide pathway may have pathological implications in the aetiology of schizophrenia.

Adult↗