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Biomedical subjects

A Thakur

Publications and source records attributed to A Thakur.

At least 19 recordsLinked to original sources
PubMed2000

Ontogeny of insulin-like growth factor 1 in a rabbit model of growth retardation.

Many cases of intrauterine growth retardation (IUGR) result from placental insufficiency, but the molecular signals accompanying this event are unknown. Insulin-like growth factor 1 (IGF-1) is a potent mitogen for fetal tissues and is lowered in the serum of human infants with IUGR. The rabbit provides an optimal model for the study of IUGR based on fetal position. To determine if IGF-1 expression is altered in the growth-retarded fetus, this naturally occurring rabbit model of IUGR was used. Four fetal rabbit pairs were harvested on Days 21, 23, 25, 27, 29, and 31 of their normal 31-day gestation; they were identified based on uterine position as normal or growth retarded. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. The SI was divided into three equal segments: proximal, middle, and distal. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. Statistical analysis was performed using ANOVA and the paired Student's t test. Weights were decreased in fetuses with IUGR at all time points (P < 0.05), further validating this rabbit model in the study of IUGR. Liver, proximal, and distal SI IGF-1 mRNA decreased during late gestation (P < 0.01). Kidney IGF-1 mRNA increased throughout late gestation (P < 0.01). Compared with their normal counterparts, fetuses with IUGR had a trend toward decreased IGF-1 mRNA in the kidney, liver, and SI at all time points, reaching significance in the liver on Day 27 (P = 0.002). Serum IGF-1 decreased throughout gestation in all fetuses (P < 0.05). Compared with normal fetuses, fetuses with IUGR had lower serum IGF-1 at all time points, reaching significance at Day 27 (P = 0.02). Amniotic fluid IGF-1 was lower in fetuses with IUGR than in normal fetuses, though not quite reaching significance. Compared with normal fetuses, growth-retarded fetal rabbits trend toward depressed liver, kidney, and intestinal expression of IGF-1 mRNA and lower serum and amniotic fluid IGF-1 protein. Serum IGF-1 levels correlate with fetal weight change. Further studies and potential manipulation of fetal IGF-1 are warranted to investigate potential prenatal intervention in the treatment of IUGR.

Amniotic Fluid↗
PubMed2000

The outcome of research training during surgical residency.

BACKGROUND/PURPOSE: Graduates of a university surgical residency program were surveyed to identify the timing of specialty selection and the impact that studying in a research laboratory had on subsequent acceptance into a fellowship program. METHODS: Between 1975 and 1990, 86 residents completed general surgery training at UCLA Medical Center. A survey was sent to all graduates to determine the focus of their previous laboratory research and when they selected their eventual surgical specialty. Responses were received from 67 of the 86 graduates (78%). RESULTS: Forty-eight of the sixty-seven respondents (72%) took one or more years of surgical research during residency. Postresidency fellowship training was selected by 55 of 67 (82%); 50 applied to fewer than five programs; 49 of 55 (89%) received one of their top three choices. Twenty-seven of the sixty-seven residents pursued an academic career (40%). Residents who performed at least 2 years of research were more likely to become academicians (53%) than residents who did 1 year or less of research (22%). Only 39 of 67 residents (58%) had selected a specialty after 2 years of clinical training; 28 more made the selection after the third clinical year. All residents interested in cardiac surgery (n = 18) or plastic surgery (n = 4) prior to research were accepted into fellowships in those specialities, whereas only 37% of those who had an interest in other fields pursued the same specialty (P < 0.0001). Residents performing research in general surgery (n = 9), surgical oncology (n = 18), cardiac surgery (n = 14), and plastic surgery (n = 3) were more likely to practice in that specialty than those doing research in other specialty laboratories. CONCLUSIONS: General surgery residents performing research in a specialty laboratory are likely to pursue fellowship training relating to that field. Those who select a career in cardiac or plastic surgery prior to research are most likely to enter into these fields as their eventual specialty. Residents who perform 2 or more years of laboratory research publish more papers and often pursue an academic career.

General Surgery↗
PubMed2000

Contact lens wear alters the production of certain inflammatory mediators in tears.

Contact lens wear has been associated with an increased risk of corneal infection and/or inflammation. We studied the hypothesis that contact lens wear alters the number of polymorphonuclear leukocytes (PMNs) on the cornea during sleep and the levels of inflammatory mediators in the tear film. Three groups of subjects were analysed: a non-contact lens wearing group (NCLW), non-adapted (neophyte) contact lens wearers (NACLW) who wore lenses during sleep for the first time in this study and adapted contact lens wearers (ACLW) who normally wore lenses on a daily wear schedule. Ocular PMNs were collected by a non-contact irrigation technique and their numbers counted after staining. Tears were collected from each group and analysed using ELISAs for the presence of the PMN chemoattractants IL-8 and LTB(4)and the cytokines IL-1beta, IL-6 and GM-CSF. Corneal irrigation data demonstrated significantly higher numbers of PMNs from NACLW (P<0.05) compared to the other groups. ACLW showed significantly fewer PMNs (P =0.03) compared to NCLW group. The NACLW group had significantly lower concentrations (P<0. 05) of IL-8, LTB(4)and IL-6 in their tears after 8 hr of sleep compared to the other groups. The ACLW group had significantly (P<0. 05) higher levels of IL-8 at most time points compared to the other two groups. The levels of the chemoattractants IL-8 and LTB(4)in tears were inversely related to the numbers of PMNs from the corneal surface and the chemotaxis of PMNs in vitro. During one night sleep in contact lenses the numbers of PMNs and the concentration of certain inflammatory mediators are significantly altered compared to no lens wear. However, this alteration changes from NACLW to ACLW. This may have effects on the ability of the eye to defend itself during contact lens wear.

Adult↗
PubMed2000

Comparison of loop versus end ileostomy for fecal diversion after restorative proctocolectomy for ulcerative colitis.

BACKGROUND: The goal of this study was to compare the benefits versus complications of temporary loop ileostomies and end ileostomies in a consecutive series of patients undergoing colectomy and ileal pouch-anal anastomosis for ulcerative colitis. STUDY DESIGN: A retrospective review was performed of all patients undergoing restorative proctocolectomy with diverting ileostomy for ulcerative colitis at the UCLA Medical Center during a 4-year period. An end ileostomy (EI) was used for 38 patients and a loop ileostomy (LI) for 39. All patients had a J pouch, with all EI patients having a hand-sewn ileoanal anastomosis, and 33 LI patients having a double-stapled anal anastomosis. EI closure was performed through a laparotomy, and LI closure was performed through a periileostomy incision. RESULTS: The mean operative time for EI closure was 157 minutes, and for LI closure was 103 minutes. The wound infection rate after EI closure was 5.3% and after LI was 10.3%. For EI patients, 2 of 38 patients required reoperation, compared with 5 of 39 for LI. The mean hospital stay after EI closure was 6.7 days, and after LI closure was 7.1 days. Peristomal skin irritation was more severe, more prolonged, and occurred in more than twice as many LI as EI patients. Home ostomy nurse care was necessary for a mean of two visits for EI patients and five visits for LI patients. The cost ofostomy supplies and care was more than double for LI patients compared with those with EI. Patient satisfaction and ability to resume physical and social activities early after ileostomy construction were much more favorable for EI than LI patients. CONCLUSIONS: The benefit of shorter operating time for LI closure compared with EI closure is often outweighed by the complications and costs of LI stomal care and patient dissatisfaction. EI should be considered more frequently for temporary ileal diversion after restorative proctocolectomy.

Adolescent↗
PubMed2000

KC production in the cornea in response to Pseudomonas aeruginosa challenge.

Pseudomonas aeruginosa can cause ulcerative bacterial keratitis. A feature of keratitis is the rapid infiltration of the avascular corneal stroma by neutrophils. KC is a potent neutrophil chemokine. The present study used a mouse model of ocular infection to assess the relationship between KC and inflammation in the cornea in response to challenge with a strain of P. aeruginosa causing keratitis. Low levels of KC mRNA and protein were detected by in situ hybridization and ELISA, respectively, in unchallenged corneas. Dramatically increased numbers of KC mRNA+ cells were present in P. aeruginosa strain 6294-challenged corneas. Expression of KC mRNA was found to be up-regulated in the corneal epithelium in response to wounding alone. The KC mRNA+ cells were located in the epithelium and corresponding to infiltrating neutrophils cells in the stroma. Quantification of KC protein at different time points showed peak levels at 8 h of bacterial challenge. These results suggest that KC may be involved with the regulation of leucocyte infiltration early during bacterial keratitis.

Animals↗
PubMed2000

Effect of dexamethasone on insulin-like growth factor-1 expression in a rabbit model of growth retardation.

BACKGROUND/PURPOSE: The maternal administration of steroids promotes fetal maturative effects in the gastrointestinal tract. To determine if fetal insulin-like growth factor-1 (IGF-1) expression is altered in response to maternal dexamethasone administration, this rabbit model of intrauterine growth retardation (IUGR) was utilized. METHODS: Eight pregnant rabbits received either dexamethasone (Dex 0.1 mg/kg/d intramuscular), or normal saline (Cont) on gestational days 26 and 27. Fetuses were harvested on gestational day 28 or 29 and were identified as favored (Fav) or runt (Runt): DexFav, DexRunt, ContFav, and ContRunt. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. RESULTS: Weight was decreased in the Runt fetuses at all time-points (P < .08). The percent weight accretion from day 28 to 29, was greatest in the DexRunt fetus (P < .001), suggesting "catch-up" growth. All Dex fetuses (Fav and Runt) had increased liver and proximal, middle and distal SI IGF-1 mRNA at day 28 and elevated levels in the liver, proximal and distal SI at day 29 compared with control fetuses. The DexRunt fetuses had serum IGF-1 protein surpassing that of the DexFav fetus at day 28. CONCLUSIONS: This report provides the first description of maternal steroid administration effecting a marked increase in fetal IGF-1 mRNA expression and IGF-1 protein levels in an in vivo rabbit model of IUGR. The growth-retarded fetus appears to be particularly responsive.

Actins↗
PubMed2000

Effect of pH and inorganic carbon concentration on growth, glycerol production, photosynthesis and dark respiration of Dunaliella salina.

The growth of Dunaliella salina was studied with respect to pH and varying concentrations of NaHCO3 in the medium. The growth rate, photosynthesis and dark respiration were maximal at pH 8 and 4 mM NaHCO3 in the medium. Photosystem I of the Hill reaction was affected more by inorganic carbon concentration than photosystem II.

Carbon Compounds, Inorganic↗
PubMed1999

Laryngeal swabs for diagnosing tuberculosis.

The value of smear and culture of laryngeal swabs as a method of confirming pulmonary tuberculosis was investigated in Indian children. A total of 116 children with 'suspected' tuberculosis had a Mantoux test and chest X-ray. Of these, 51 had a positive Mantoux and/or chest X-ray compatible with tuberculosis, and this group had two laryngeal swabs taken on each of 3 consecutive days. The Mantoux test was positive in 37 (73%) of the 51 'probable' cases. Chest X-ray was abnormal in 36 (71%) cases and compatible with tuberculosis in 20 (39.7%). Mycobacterium tuberculosis was cultured from laryngeal swabs in 14 (28%) children and in another three children smears were positive but culture-negative. The overall confirmation rate for tuberculosis was 33%. Laryngeal swabs are a simple method of confirming tuberculosis and may be undertaken in out-patients.

Adolescent↗
PubMed1999

Familial resemblance in humoral immune response to defined and crude Schistosoma mansoni antigens in an endemic area in Brazil.

This study addressed whether the humoral immune response to crude and defined Schistosoma mansoni antigens aggregates within families. The sample included 155 siblings from 42 nuclear families in Brazil. Sera examined by ELISA for antibody isotypes reactive to defined schistosome antigens and crude schistosome antigens (soluble adult worm antigen preparation and soluble egg antigen) demonstrated that there was a difference in sibling-pair correlations between defined and crude S. mansoni antigens. In contrast to the finding with crude antigens, egg-positive sibling pairs showed significant familial resemblance for all IgG subclasses and IgE to adult-stage antigens Smp20.8 and Smp50. Only the IgE and IgG4 isotypes showed familial resemblance to the egg-stage antigen, Smp40. Egg-negative sibling pairs showed significant familial resemblance only for IgE and IgG4 to Smp40. That both the IgE and IgG4 response to defined S. mansoni antigens showed familial resemblance is interesting in light of the converging evidence for the role of IgE and IgG4 in human susceptibility and resistance to reinfection.

Adolescent↗
PubMed1999

Port-wine-stain (nevus flammeus), congenital Becker's nevus, café-au-lait-macule and lentigines: phakomatosis pigmentovascularis type Ia--a new combination.

A 16-year-old male had brown macules in a geographic pattern with increased terminal hair on the back and dusky red partially blanchable non progressing macules on his left thigh since birth. Clinical diagnoses of Becker's nevus and port-wine-stain were made and confirmed histopathologically. In addition, he had multiple lentigines on the face and trunk and a single café-au-lait-macule on his chest.

Adolescent↗
PubMed1998

Chemotactic activity of tears and bacteria isolated during adverse responses.

Inflammatory processes are characterized by the dynamic influx of leukocytes. This leukocyte recruitment and activation is thought to be initiated by chemical signals including chemotactic factors. This study was designed to investigate the chemotactic activity in different tear types and bacteria isolated during adverse responses to contact lens wear. Chemotactic activity was determined by quantitating in vitro neutrophil migration using a microchemotaxis chamber. Results demonstrated that tears collected immediately after 8 hours sleep (P<0.001) and tears collected during adverse responses (P<0.001) showed significantly higher chemotactic activity compared to reflex tears. Specific neutralizing antibodies to IL-8, LTB4 and C5a were added to closed eye and adverse response tears. Pre-incubation of closed eye tears with antibodies to IL-8 showed a significant reduction in chemotactic activity (P<0.0001), whereas a significant reduction of PMN migration in adverse response tears was observed after pre-treatment with antibodies to LTB4 (P<0.0001). However no difference in chemotactic activity was observed after incubation with antibody to C5a or irrelevant antibody. Dot blots demonstrated that closed eye tears contained approximately 150 ng ml-1 IL-8 and adverse response tears contained 2 ng ml-1 IL-8. Most Gram negative bacteria isolated from contact lenses caused directed migration of PMNs. Addition of neutralizing antibody to LPS significantly abrogated the chemotactic activity of bacterial cells (P<0.001). Our findings provide evidence that IL-8 during eye closure, and bacterial chemotactic substances and LTB4 during contact lens induced adverse responses, are responsible for the recruitment of PMNs.

Chemotaxis, Leukocyte↗
PubMed1998

Cytokine and lipid inflammatory mediator profile of human tears during contact lens associated inflammatory diseases.

Contact lens induced acute red eye (CLARE) and contact lens induced peripheral ulcer (CLPU) are among the most common contact lens induced inflammatory reactions. Both CLARE and CLPU are characterized by corneal infiltration which indicates the presence of chemoattractants and other inflammatory mediators. The aim of this study was to characterize the cytokine and chemotactic lipid inflammatory mediator profile in the tears of people experiencing CLARE or CLPU. Cytokines IL-1 beta, IL-6, IL-8, GM-CSF and LTB4 in tears were measured by antibody sandwich and competition inhibition enzyme-linked immunosorbent assays (ELISA). Platelet activating factor-like activity was measured by a degranulation assay by measuring the release of labelled serotonin from platelets. The functional role GM-CSF and chemoattractants were determined by flow cytometry and chemotaxis. Increased levels of cytokines and chemoattractants were detected in both CLARE and CLPU tears. CLPU tears showed increased levels of LTB4 (P = 0.002) and PAF-like activity (P = 0.047) whereas CLARE tears showed increased levels of GM-CSF (P = 0.002). IL-8 (P < 0.05). LTB4 (P = 0.002) and PAF-like activity (P = 0.047) compared to control tears. Flow cytometric analysis revealed that incubation of PMN with CLARE tears increased the number of IgA receptors indicating that the GM-CSF in CLARE tears was active. Combinations of suboptimal concentrations (which were found in CLARE and CLPU tears) of IL-8 with either LTB4 or PAF significantly (P < 0.0001) enhanced the chemotactic activity for PMN compared to their individual effects. Our data highlight the possible pathophysiological roles of these inflammatory mediators in leukocyte recruitment and activation during ocular inflammatory responses. The results suggests that GM-CSF, IL-8 and LTB4 are active during corneal pathology and LTB4 or IL-8 may maintain the contact lens induced PMN response in vivo.

Acute Disease↗
PubMed1998

The proinflammatory cytokines and arachidonic acid metabolites in human overnight tears: homeostatic mechanisms.

The tear film plays an important role in the defense of the external ocular surface. During sleep a number of changes take place, including increased production and release of various inflammatory mediators. We have studied the hypothesis that closed-eye tears contain proinflammatory cytokines and lipid inflammatory mediators, which serve to recruit polymorphonuclear leukocytes (PMNs) and regulate the function of PMNs and IgA during sleep. We investigated interleukin-1beta, interleukin-6, interleukin-8, monocyte chemotactic protein 1, granulocyte-macrophage colony stimulating factor (GM-CSF), leukotriene B4 (LTB4), and platelet activating factor (PAF) in open and closed-eye tears of normal healthy subjects. Results showed that IL-6, IL-8, GM-CSF, LTB4, and PAF were present in high levels in closed-eye tears compared to open-eye tears. Closed-eye tears were able to recruit neutrophils, with maximal recruitment after 8 hr of sleep, suggesting that chemokine IL-8 and the lipid chemoattractant LTB4 were active. Flow cytometric analysis revealed that incubation of neutrophils with closed-eye tears up-regulated the surface expression of IgA receptor, indicating that the GM-CSF in tears was functionally active. Up-regulation of cytokines and the lipid inflammatory mediator LTB4 during eye closure are noteworthy, as each of these cytokines has an established role in initiation and amplification of the inflammatory response. IL-8 and LTB4 may act as potent chemoattractants and activators for PMNs, whereas IL-6 and GM-CSF potentiate the secretion and function of IgA and enhance neutrophil responsiveness to proinflammatory agonists.

Adult↗
PubMed1998

Interactions between Candida species and platelets.

Candida spp. are able to cause disseminated disease in immunocompromised patients. This study examined the interactions of Candida spp. with platelets, complement and polymorphonuclear leucocytes (PMNLs). With the exception of C. albicans, all other Candida spp., including a C. albicans strain previously classified as C. stellatoidia, aggregated human platelets at a ratio of yeast cells: platelets of 1:80. Usually, those species and strains that aggregated platelets were either killed or prevented from growing in platelet-rich plasma indicating that the aggregation released microbicidal or microbistatic substances that were active against Candida spp. All Candida spp. were resistant to attack by complement in 50% serum. However, all species activated complement as determined by the presence of C3 fragments on their surface, in particular a 195-kDa fragment corresponding to C3c, two fragments at 67 and 40 kDa corresponding to iC3b, and a 33-kDa fragment corresponding to C3d. When strains were tested for their ability to stimulate the release of pro-inflammatory substances from platelets and PMNLs, it was found that most strains stimulated PMNLs to release interleukin(IL)-8 but not IL-1beta or leucotriene B4. The ability of C. albicans to evade complement-mediated killing and not to aggregate platelets may contribute to the survival of this species in the blood during vascular infections.

Anticoagulants↗