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Biomedical subjects

A Upadhyaya

Publications and source records attributed to A Upadhyaya.

10 recordsLinked to original sources

Neutrophil chemorepulsion in defined interleukin-8 gradients in vitro and in vivo.

We report for the first time that primary human neutrophils can undergo persistent, directionally biased movement away from a chemokine in vitro and in vivo, termed chemorepulsion or fugetaxis. Robust neutrophil chemorepulsion in microfluidic gradients of interleukin-8 (IL-8; CXC chemokine ligand 8) was dependent on the absolute concentration of chemokine, CXC chemokine receptor 2 (CXCR2), and was associated with polarization of cytoskeletal elements and signaling molecules involved in chemotaxis and leading edge formation. Like chemoattraction, chemorepulsion was pertussis toxin-sensitive and dependent on phosphoinositide-3 kinase, RhoGTPases, and associated proteins. Perturbation of neutrophil intracytoplasmic cyclic adenosine monophosphate concentrations and the activity of protein kinase C isoforms modulated directional bias and persistence of motility and could convert a chemorepellent to a chemoattractant response. Neutrophil chemorepulsion to an IL-8 ortholog was also demonstrated and quantified in a rat model of inflammation. The finding that neutrophils undergo chemorepulsion in response to continuous chemokine gradients expands the paradigm by which neutrophil migration is understood and may reveal a novel approach to our understanding of the homeostatic regulation of inflammation.

Animals↗

TFIIAalpha/beta-like factor is encoded by a germ cell-specific gene whose expression is up-regulated with other general transcription factors during spermatogenesis in the mouse.

TFIIAalpha/beta-like factor (ALF) is a testis-specific counterpart of the large subunit of human general transcription factor TFIIA. Northern analysis shows that ALF mRNA first appears in mouse testis at Postnatal Day 14. Similarly, expression of the general transcription factors TBP, TRF2, TFIIAalpha/beta, TFIIAgamma, and TFIIIB(90) is also increased beginning at Postnatal Day 14, suggesting that there is a coordinated induction of many general transcription factors during male germ cell differentiation. Analysis of male germ cells separated by Staput sedimentation shows that ALF is present in pachytene spermatocytes and haploid spermatids. In addition, in situ hybridization experiments with adult mouse testis shows that ALF is present in haploid spermatids. Searches of the human genome sequence database using the basic local alignment search tool reveal that the ALF and TFIIAalpha/beta(GTF2A1) genes are both composed of nine exons, whereas the TFIIAgamma (GTF2A2) gene is composed of five exons. Furthermore, nucleotide and amino acid comparisons among human and mouse ALF, TFIIAalpha/beta, and TFIIAgamma cDNA sequences show that ALF has diverged more rapidly than either TFIIAalpha/beta or TFIIAgamma. Finally, the ALF and SBLF (Stoned B-Like Factor) sequences present in the chimeric SALF cDNA are both present on human chromosome 2, and an analysis of the corresponding genes suggests a model for the formation of SALF.

Amino Acid Sequence↗

Anti-invasive, antitumorigenic, and antimetastatic activities of the PHSCN sequence in prostate carcinoma.

Using naturally serum-free SU-ECM basement membranes as invasion substrates showed that plasma fibronectin was necessary to stimulate invasion by DU 145 human and metastatic MATLyLu (MLL) rat prostate carcinoma cells. This activity mapped to the PHSRN sequence, which induced invasion through alpha5beta1 integrin. PHSCN, a competitive inhibitor, blocked both PHSRN- and serum-induced invasion. Acetylated, amidated PHSCN (Ac-PHSCN-NH2) was 30-fold more potent; however, Ac-HSPNC-NH2 was inactive. Rats receiving injections s.c. with 100,000 MLL cells were treated systemically by i.v. injection three times weekly with 1 mg of either Ac-PHSCN-NH2 or Ac-HSPNC-NH2 beginning 24 h later, three times weekly with 1 mg of Ac-PHSCN-NH2 beginning only after surgery to remove large (2 cm) MLL tumors, or were left untreated. MLL tumors grew rapidly in Ac-HSPNC-NH2-treated and in untreated rats. MLL tumor growth in rats treated with Ac-PHSCN-NH2 beginning 1 day after MLL cell injection was reduced by 99.9% during the first 16 days of treatment, although subsequent tumor growth occurred. MLL tumor cryosections immunostained with anti-PECAM-1 showed that Ac-PHSCN-NH2 inhibited neovascularization by 12-fold during this time. Whether initiated after MLL cell injection or only after MLL tumor removal, Ac-PHSCN-NH2 treatment reduced the numbers of MLL lung colonies and micrometastases by 40- to >100-fold, whereas Ac-HSPNC-NH2 was inactive. Thus, Ac-PHSCN-NH2 may be a potent antitumorigenic and antimetastatic agent for postsurgical use prior to extensive metastasis.

Amino Acid Sequence↗

Diffusion and deformations of single hydra cells in cellular aggregates.

Cell motion within cellular aggregates consists of both random and coherent components. We used confocal microscopy to study the center of mass displacements and deformations of single endodermal Hydra cells in two kinds of cellular aggregates, ectodermal and endodermal. We first carefully characterize the center of mass displacements using standard statistical analysis. In both aggregates, cells perform a persistent random walk, with the diffusion constant smaller in the more cohesive endodermal aggregate. We show that a simple parametric method is able to describe cell deformations and relate them to displacements. These deformations are random, with their amplitude and direction uncorrelated with the center of mass motion. Unlike for an isolated cell on a substrate, the random forces exerted by the surrounding cells predominate over the deformation of the cell itself, causing the displacements of a cell within an aggregate.

Animals↗

Physiologic and neuroendocrine responses to intravenous naloxone in subjects with Alzheimer's disease and age-matched controls.

BACKGROUND: Prior work showed that administration of naloxone HCl had different behavioral effects in patients with Alzheimer's disease (AD) than controls. The aim of the present study was to contrast the physiologic and neuroendocrine responses to administration of a wide range of doses of intravenous naloxone of patients with probable Alzheimer's disease to aged-matched controls. METHODS: This was a double-blind, placebo-controlled, study of 12 patients with probable Alzheimer's disease and 8 age-matched normal controls who each received intravenous infusions of naloxone HCl on 3 different days in doses of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg. Order of treatment condition was randomized. Vital signs and plasma cortisol and prolactin were obtained at regular intervals. RESULTS: Both groups showed increased cortisol after naloxone 0.1 mg/kg and 2.0 mg/kg (p < .0001), but the increase was significantly greater and longer lived in controls than in patients. Patients, but not controls, also experienced a significant hypothermic response after naloxone 2.0 mg/kg (p < .05). Prolactin, heart rate, and blood pressure did not change following naloxone and did not differ between groups. CONCLUSIONS: These findings support a growing body evidence that HPA axis activity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition.

Adult↗

Hepatitis B subtypes and hepatitis C genotypes in cirrhosis in western India: results of a pilot study.

BACKGROUND: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are the major causes of viral chronic liver diseases in India. HBV subtypes and HCV genotypes have not been reported from Western India. The aims of the study were (i) To study the prevalence of viral markers to HBV and HCV in adult cirrhotics, (ii) To determine HBV subtypes and HCV genotypes using serological and molecular biological methods. METHODS: A total of 99 adult cirrhotic patients, proven by liver biopsy, laparoscopy, or a combined score of clinical features, biochemical tests, ultrasonography of abdomen, and radioisotope 99m Technetium scan in presence of oesophageal varices were studied. Sera collected from these patients were stored at -8 degrees C and subjected to various tests. HBsAg was determined by ELISA, anti-HBc by ELISA and anti HCV Ab was determined by the third generation ELISA. HBsAg subtypes were determined by enzyme immunoassay. HCV RNA was determined by PCR in those who tested positive for anti HCV antibody. Genotyping of HCV was done with a second generation PCR. RESULTS: HBsAg was detected in 16, out of which subtyping was possible in 14, adw was found in 6 and ayw in 8. Anti HCV Ab was found in 5. Genotyping was possible in three samples which revealed one to be of genotypes 3, one of genetic group 4, and one of genetic group 5. CONCLUSIONS: Subtypes and genotypes of HBV and HCV have not been reported from Western India. Their determination can have implications in understanding the spectrum of disease, characteristics and response to treatment.

Adolescent↗

Psychiatric morbidity among mothers attending well-baby clinic: a cross-cultural comparison.

The Self Reporting Questionnaire (SRQ), a screening instrument developed for psychiatric disorders in developing countries, was administered to 149 mothers, half of whom where non-white, attending a well-baby clinic in Manchester, United Kingdom. Psychiatric interview confirmed that high scorers on the SRQ could be given DSM-III diagnoses of anxiety and depression, but the cut-off point on SRQ for being a definite psychiatric case was found to be 7/8, higher than previous validation studies. This was the same for Asians as well as white mothers. Comparison of somatic versus psychological scores between Asian and white mothers showed no significant difference across the range of total SRQ scores. Over half of the mothers who were psychiatric cases were attending their doctors and all the Asian women doing so were attending for somatic symptoms. This study suggests that when measured in a well-baby clinic, somatic and psychological symptoms are reported equally frequently by white and Asian immigrant women in the United Kingdom but somatic symptoms predominate when Asian women consult a doctor.

Adult↗

Poor seroconversion rate after hepatitis B vaccination in high-risk institutionalized mentally retarded patients.

We studied the rate of seroconversion to positivity for antibody to hepatitis B surface antigen (anti-HBs) after immunization with hepatitis B vaccine in a group of mentally retarded institutionalized patients. Eight hundred sixty-eight individuals were screened for seromarkers of hepatitis B infection (hepatitis B surface antigen and anti-HBs), and 287 seronegative patients were vaccinated with the recommended schedule of hepatitis B virus vaccine (20 micrograms IM at 0, 1, and 6 months). Overall, 59% of patients responded to vaccination with detectable anti-HBs. We found a high correlation of lack of response with both intragluteal injection and increasing age (p less than 0.0008), although the design of the study did not allow these factors to be analyzed separately. We conclude that buttock injection and advancing age may be risk factors for poor immunogenicity of the hepatitis B vaccine in mentally retarded populations.

Adult↗

Beta-blockers in the severely and profoundly mentally retarded.

The authors present data from four different institutions from open clinical trials of propranolol in 19 mentally retarded patients with IQs less than 50. When customary forms of treatment had failed, propranolol was initiated. A table showing changes in the patients' behavior is included. Twelve patients demonstrated a pronounced improvement in self-abusive and aggressive behavior, four made moderate gains, and three were considered unchanged. The authors postulate that at least some aspects of the behavioral improvement were due to the peripheral anxiolytic action of the beta-blockers. Contrary to other reports of using higher doses (greater than 520 mg/day range), the authors used a mean dose of 120 mg/day and consider the duration of time spent on the medication as a crucial factor in its effectiveness.

Adrenergic beta-Antagonists↗