Biomedical subjects
Publications and source records attributed to A Kaul.
Extraadrenal paragangliomas are very rare tumors arising from cells derived from the neural crest. These tumors are encountered only as case reports, and as a result, little is known of their natural history. We present a case of pancreatic paraganglioma and review all previously reported cases.
Steroid receptors mediate responses to lipophilic hormones in a tissue- and ligand-specific manner. To identify nonreceptor proteins that confer specificity or regulate steroid signaling, we screened a human cDNA library in a steroid-responsive yeast strain. One of the identified cDNAs, isolated in the screen as ligand effect modulator 6, showed no homology to yeast or Caenorhabditis elegans proteins but high similarity to the recently described mouse coactivator PGC-1 and was accordingly termed hPGC-1. The hPGC-1 DNA encodes a nuclear protein that is expressed in a tissue-specific manner and carries novel motifs for transcriptional regulators. The expression of hPGC-1 in mammalian cells enhanced potently the transcriptional response to several steroids in a receptor-specific manner. hPGC-1-mediated enhancement required the receptor hormone-binding domain and was dependent on agonist ligands. Functional analysis of hPGC-1 revealed two domains that interact with steroid receptors in a hormone-dependent manner, a potent transcriptional activation function, and a putative dimerization domain. Our findings suggest a regulatory function for hPGC-1 as a tissue-specific coactivator for a subset of nuclear receptors.
BACKGROUND: Leptin is an important regulator of food intake and energy expenditure. Initially it was thought to be expressed exclusively in and secreted by adipocytes. Recently, leptin expression was also noted in other tissues, including rat gastric mucosa. Information on leptin and leptin receptor expression in the human stomach is lacking. AIM: To investigate expression of leptin and its corresponding receptors in human gastric epithelial cells. METHODS: Fundic and antral gastric mucosal biopsies, primary cultures of human gastric epithelial cells, and the human gastric cancer cell line AGS were screened for expression of leptin and different leptin receptor isoform mRNA by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed for localisation of leptin and leptin receptor proteins in gastric mucosa. RESULTS: mRNA of leptin and its four receptor isoforms (huOB-R, long receptor isoform; huB219.1-3, short receptor isoforms) was detected in gastric mucosal biopsies, cultured human gastric epithelial cells, and gastric cancer cells. Immunohistochemistry demonstrated that chief as well as parietal cells were reactive to leptin and leptin receptors. CONCLUSIONS: Leptin and leptin receptors are expressed in human gastric mucosa. These findings suggest a paracrine and/or autocrine effect of leptin on gastric epithelial cell function.
OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.
Foam separation is known to have potential for separation of biological molecules with a range of surface activities. A statistical study (factorial design) was carried out to establish the optimum operating conditions for the continuous foam separation of beta-casein. Maximum values of enrichment of beta-casein into the foam phase were found for low levels of initial feed protein concentration, gas flow rate, feed-flow rate, and high foam heights. Maximum values of protein recovery, were generally found at high levels of initial feed protein concentration, gas-flow rate, feed-flow rate, and low foam heights. The highest values obtained for enrichment and separation ratio were 54.7 and 181.3, respectively, with a simultaneous protein recovery of 62%; thus, illustrating the potential effectiveness of this technique. The effect of foaming on protein conformation is also important, and in this study protein structure was analyzed before and after foam separation experiments. Techniques used were: native polyacrylamide gel electrophoresis (PAGE), UV absorbance spectroscopy, circular dichroism, and fluorescence. Native PAGE showed no detectable changes in protein structure. However, absorbance scanning, fluorimetry, and circular dichroism revealed some conformational changes over a range of concentration effects.
Foam separation may have potential for protein recovery. However, for foam separation to be a viable protein recovery technique it is important to demonstrate, not only that high enrichments and recoveries can be achieved for single proteins, but also that high enrichments and recoveries, together with selectivity of partition, can be achieved for recovery from multi-component mixtures. Most process streams which require purification are indeed complex multi-component mixtures, for example, fermentation broths. In this study, three binary protein mixtures were chosen for continuous foam separation: beta-casein:lysozyme; Bovine serum albumin (BSA):lysozyme and beta-casein:BSA (mixtures 1, 2, and 3, respectively). For each of these mixtures, the expected outcome of each experiment, based on a previous knowledge and determination of relevant protein physical properties, was that the first protein should be preferentially separated into the foam phase. On the basis of results reported in Part I of this study for the continuous foam separation of beta-casein, conditions found to favor maximum enrichment were selected. For each mixture a range of concentrations of both proteins was considered. For mixture 1, maximum protein recoveries in the foam phase were 85.6% and 25% for beta-casein and lysozyme, respectively; and for mixture 2, maximum recoveries of 77. 6% and 18.9% were obtained for BSA and lysozyme, respectively. Maximum enrichment ratios in the foam phase were 79.4 and 2.5 for beta-casein and lysozyme respectively in mixture 1; and 74.0 and 1.4 for BSA and lysozyme respectively in mixture 2. Selective partitioning of beta-casein and BSA into the foam phase was obtained in mixtures 1 and 2, respectively, particularly for protein concentrations at which dilute protein films are known to form at the gas-liquid interface in the foam. Maximum partition ratios for mixtures 1 and 2 were 31.8 and 52.8, respectively. For mixture 3, both BSA and beta-casein were enriched into the foam phase. Maximum enrichments were 42.9 and 24.7 for BSA and beta-casein, respectively; however, selective partitioning in mixture 3 was limited (maximum partition ratio being 1.8).
We present a case of an in-situ lobular carcinoma within an otherwise benign fibroadenoma in a 45-year-old woman.
Naturally occurring plant polyphenols, which include ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA), were tested for their superoxide anion radical (SOR)-scavenging activities. SOR were produced by interaction of the tumor promoter benzoyl peroxide (BPO) with murine peritoneal macrophages in vitro. The levels of SOR were assessed microscopically by counting the number of formazan-positive cells per 250 cells produced by the reduction of nitro blue tetrazolium. BPO at a concentration of 15 micrograms/1.85 x 10(6) cells/0.5 ml induced maximum formation of SOR in resident and thioglycollate-elicited cells. All the tested polyphenols were able to inhibit the formation of SOR induced by the tumor promoter to a variable degree. Inhibition of BPO-induced SOR formation by polyphenols was in the following order: FA > TA > CA > EA. BPO stimulated the accumulation of diacylglycerol (DAG) in resident and elicited macrophages with concurrent release of choline equivalents from macrophages. Polyphenols inhibited DAG accumulation, which paralleled the inhibition of choline equivalent release. FA was observed to be the most effective and EA the least effective inhibitor of SOR formation, DAG accumulation, and release of choline equivalents. It is likely that inhibition of SOR formation might be due to some interference in the cellular lipid metabolism and phospholipid equivalent deacylation and choline release.
Phenytoin (PHT) is a widely prescribed antiepileptic drug. Its potential to interact with genetic material was investigated in a set of 30 epileptic patients (age 10-30 years) prior to and following the administration of PHT over a period of 9 months (grouped in a multiple of 3 months) and 40 control subjects in relation to age, sex, duration of drug therapy, and plasma concentration of PHT, using the sister chromatid exchange (SCE) frequency assay. Plasma levels of the phenytoin were measured by biochemical assay in epileptic patients before and after the PHT therapy. The peripheral blood lymphocytes were cultured and harvested at 72 h. The frequency of SCE was significantly higher (P < 0.001) in both age groups (10-20 and 21-30 years) for PHT-treated epileptics compared to PHT-untreated and control subjects. However, there were no considerable variations in SCE finding between the control and PHT-untreated patients. Between the two age groups, a significantly higher SCE frequency was observed in PHT-treated patients (P < 0.01) in the older age group (21-30 years). Mean SCE frequency did not differ between the male and female in the controls, PHT-untreated, or treated epileptics. Correlation between the plasma concentration of PHT and the incidence of SCE among 30 patients was insignificant. PHT monotherapy appears to have genotoxic effect as expressed by the induction of increased SCE rates in treated epileptics, while disease does not play any role in inducing genetic damage as shown by no difference in SCE frequencies between control subjects and PHT-untreated epileptic patients.
The mitotic index and proliferation rate index were investigated to determine the effect of phenytoin (PHT) in cultured blood lymphocytes of epileptics prior to and following administration of PHT over a period of 9 months (grouped in multiples of 3 months) and 40 control subjects (age range 10-30 years). Treatment with PHT brought inhibition of the mitotic index (MI) and proliferation rate index (PRI), which were significantly higher in treated subjects or which were more expressive in treated lymphocytes (P < 0.001) for all the three durations of treatment. In addition, statistically significant heterogeneity of first, second, and third metaphases between the treated, untreated, and control subjects was found. Mean PRI values were used to estimate cell cycle delays, showing the highest effect in treated lymphocytes (P < 0.001). There was no considerable variation between the control and untreated (P > 0.05). The study demonstrates that PHT may be potentially genotoxic and hence the usefulness of MI and PRI in monitoring epileptics on anticonvulsant treatment.
We retrospectively reviewed the charts of 54 human immunodeficiency virus (HIV) infected patients or acquired immunodeficiency syndrome (AIDS), who were hospitalized at the Bronx-Lebanon Hospital Center with acute pancreatitis between January 1993 and December 1995. Nineteen were female and 35 were male patients. Thirty-five (65%) of 54 patients were younger than 40 years (average age, 42 years). Forty-eight (89%) of the patients had a CD4 count of <200 units/ml of blood. Seventeen (32%) patients died either of complications of acute pancreatitis or of underlying disease. The conventional prognostic criteria used to assess the severity of pancreatitis, including Ranson's and Imrie's criteria and the APACHE II system, were applied. We determined that these criteria were not appropriate to our HIV/AIDS patients. Only serum calcium levels at 48 h after admission and serum creatinine and blood urea nitrogen (BUN) at admission and at 48 h after admission had significant p values (<0.05). We believe that the predictors commonly used to identify the severity of pancreatitis were not useful in these patients because of their low CD4 counts and preexisting liver and renal disease.
The German Thorotrast study comprises 2,326 patients and 1,890 controls. Forty-eight Thorotrast patients and 239 controls are still alive and are invited for a follow-up examination every 2 years. In the deceased patients, the following neoplastic diseases with excess rates were registered (Thorotrast/controls): liver cancer (454/3); cancer of the bile ducts, including gallbladder (42/7); myeloid leukemia (40/7); myelodysplastic syndrome (30/4); plasmacytoma (10/2); non-Hodgkin's lymphoma (15/5); bone sarcoma (4/1); malignant peritoneal or pleural mesothelioma (9/0). Dose calculations are based on results of whole-body counting, X-ray films, and data obtained from the hospital records on the volume of Thorotrast injected. For liver cancer, the cumulative risk estimate was calculated to be 40 per 10(4) person Sv (radiation weighting factor = 20). These figures are close to the results of the Danish study and are comparable to the results of the Life Span Study of A-bomb survivors after 40 years at risk with 18 to 48 liver cancers per 10(4) person Sv. For hematopoietic malignancies, the cumulative risk was calculated to be about 7 per 10(4) person Sv (radiation weighting factor = 20). This risk estimate is lower by a factor of 10 compared to the results of the Life Span Study.
Two separation techniques, foam separation and colloidal gas aphrons (CGAs), both of which are based on gas-liquid dispersions, are compared as potential applications for protein recovery in downstream processing. The potential advantages of each method are described and the concentration and selectivity achieved with each method, for a range of proteins is discussed. The physical basis of foam separation is the preferential adsorption of surface active species at a gas-liquid interface, with surface inactive species remaining in bulk solution. When a solution containing surface active species is sparged with gas, a foam is produced at the surface: this foam can be collected, and upon collapse contains surface active species in a concentrated form. CGAs are microbubble dispersions (bubble diameters 10-100 microm) with high gas hold ups (>50%) and relatively high stability, which are formed by stirring a surfactant solution at speeds above a critical value (typically around 5000 rpm). It is expected that when proteins are brought into contact with aphrons, protein adsorbs to the surfactant through electrostatic and/or hydrophobic forces. The aphron phase can be separated easily from the bulk solution due to its buoyancy, thus allowing separation of protein in a concentrated form.
Ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA) offer considerable promise as anticarcinogens. The role of these dietary polyphenols was investigated in the promotional phase of carcinogenesis. Topical application of polyphenols simultaneously with phorbol-12-myristate-13-acetate (PMA) or mezerein resulted in significant protection against 7,12-dimethyl-benz[a]anthracene-induced skin tumors in mice. Caffeic acid was the most effective inhibitor of tumor promotion. In vivo and in vitro treatment of murine peritoneal macrophages with the tumor promoters resulted in stimulation of superoxide anion radical formation. Tannic acid, caffeic acid, and ferulic acid were stronger inhibitors of PMA- and mezerein-induced superoxide anion radical than ellagic acid in in vivo and in vitro conditions. Treatment of [1(3)-14C]glycerol- or [methyl-14C]choline chloride-labeled resident or thioglycollate-elicited macrophages with PMA and mezerein led to accumulation of radioactive diacylglycerol equivalents. The polyphenols were capable of inhibiting these releases.
Children with gastrointestinal motility disorders present with diverse symptoms, and obtaining a detailed history is often impossible. As in adults, evaluation of a suspected motility disorder begins with exclusion of mechanical obstruction or primary inflammatory disorders. Subsequently, coordination of peristaltic function is evaluated in those segments of the gastrointestinal tract that are suspected to be abnormal based on the clinical history. Evaluation of gastrointestinal motility in children is particularly challenging because of frequent lack of patient cooperation and difficulties in adapting the equipment to patient size. This review discusses the indications and approach to the evaluation of motility of each region of the gastrointestinal tract in infants and children.
Escherichia coli that express Dr fimbriae and related adhesins recognize the common receptor decay accelerating factor. E. coli strains that express adhesins of the Dr family were postulated to be associated with cystitis (30-50%), pregnancy-associated pyelonephritis (30%), and chronic diarrhea (50%). In this study, we investigated the hypothesis that E. coli renal interstitial binding mediated by the Dr adhesin may be important for the development of chronic pyelonephritis. An insertional dra mutant, E. coli DR14, of the clinical E. coli isolate IH11128 bearing Dr fimbriae, was constructed and used to characterize persistence of infection and interstitial tropism in an experimental model of ascending pyelonephritis. Quantitative cultures of kidney homogenates indicated that Dr hemagglutinin positive (Dr+) E. coli IH11128 established a 1-yr colonization of renal tissue. In the Dr hemagglutinin negative (Dr-) group, 50% of animals cleared infection within 20 wk and 100% between 32 to 52 wk. Dr+ E. coli colonized the renal interstitium. Significant histological changes corresponding to tubulointerstitial nephritis including interstitial inflammation, fibrosis, and tubular atrophy were found in the kidney tissue of the Dr+ but not the Dr- group. A substantial amount of fimbrial antigen was detected in the parenchymal regions affected by interstitial inflammation and fibrosis. The obtained results are consistent with the hypothesis that mutation within the dra region, affecting E. coli binding to tubular basement membranes, prevented renal interstitial tropism and the development of the changes characteristically seen in tubulointerstitial nephritis.
The exposure of the German population to man-made radiation results mainly from diagnostic X-ray and nuclear medical examinations. Data are presented about the annual frequency and the average dose of the various examination types for West Germany in the years 1990-1992. According to these data a yearly average of approximately 1550 diagnostic examinations using ionizing radiation were performed per 1000 inhabitants resulting in an annual per caput effective dose of 1.9 mSv. Despite the frequent use of alternative examination techniques, such as sonography, nuclear magnetic resonance and endoscopy, the frequency of X-ray and nuclear medical examinations is still increasing. If collective risk assessments are done using the per caput effective dose, at least the age distribution of the patients must be considered. This leads to a "risk-modifying factor" of 0.6-0.7 for patients to be applied to the ICRP risk coefficient of 5 % per Sv valid for the general population. However, radiation risk must always be viewed in context with disease- and therapy-related risks and balanced against the benefit of the diagnostic examination, which should always exceed the risk for a well-indicated procedure.
OBJECTIVE: Radiofrequency catheter ablation of atrial tachycardias and flutter is an established technique. The same modality in the microbipolar mode is effective in producing full thickness coagulation injury. Cox's maze procedure is highly successful in curing atrial fibrillation (AF) surgically. However, it consumes relatively long cross clamp time and cardiopulmonary bypass time. In this study, radiofrequency microbipolar coagulation was used as an adjunct to corrective valve surgery, as an intraoperative ablative modality to replace Cox's maze III incisions, thus remarkably shortening the procedure. The results of this procedure are compared historically with those of 26 patients who underwent corrective valve surgery alone. METHODS: Radiofrequency microbipolar coagulation was used to produce conduction blocks along the Cox's maze III incision lines as an adjunct to valve surgery in 18 patients in atrial fibrillation undergoing surgery for rheumatic valvular disease. A bayonet type bipolar forceps with an active tip length of 7 mm drawing current from a microbipolar port of Valleylab Force 4 electrosurgical unit (Valleylab, Boulder, CO) was used for microbipolar coagulation. A 3-mm retinal handheld cryoprobe working on nitrous oxide gas was used for cryoablation. RESULTS: A total of 15 survivors in the coagulation maze group were followed from 43 to 224 days (149.7 +/- 73.1 mean +/- S.D.). Twelve of the 15 survivors (80%) converted to normal sinus rhythm (70% confidence limit: 64.7-90.6%). Atrial transport function studies with pulsed wave doppler, showed presence of a wave in all the 12 (100%) patients in tricuspid valve flow and in nine (75%) patients in mitral valve flow. The procedure took 11.62 +/- 3.86 min of elective cardioplegic arrest time for the left atrial portion and 18.71 +/- 4.25 min of cardiopulmonary bypass time during reperfusion for the right atrial portion. Of the 23 survivors out of 26 patients who underwent the valve procedure alone, only one patient (4.3%) converted to normal sinus rhythm (70% confidence limit: 0.6-14%). CONCLUSION: Thus, our modification considerably shortened the time taken for creating the maze in comparison to the Cox's maze procedure and was effective in restoring normal sinus rhythm in 80% of the patients.