Primary hypertrophic osteoarthropathy.
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Biomedical subjects
Publications and source records attributed to S Banerjee.
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The present study reports the chemopreventive potential of the oil from mustard seed on 7,12-dimethylbenz[a]anthracene-induced transplacental and translactational carcinogenesis in Swiss albino mice. Gestating females were treated with mustard oil at dose levels of 0.05 and 0.10 ml per day from days 13 to 19 of gestation. In addition, they were given DMBA (3 mg/animal) on days 15-17 of gestation. The percentage of tumour incidence in the F1 progeny was reduced significantly at both dose levels from 65% in the control group to 29% and 16%, respectively, in the experimental groups. The mean number of tumours per effective F1 progeny was reduced from 1.56 in the control group to 0.93 and 0.41 in the animals treated with lower and higher doses of mustard oil, respectively. When lactating mothers were given the mustard oil at dose levels of 0.05 and 0.10 ml per day for the first 15 days of lactation in addition to DMBA given on days 3, 6, 9, 12 and 15 of lactation, the multiple site tumour incidence was brought down significantly from a control value of 70% to 32% and 18%, respectively, in lower and higher dose groups. The mean number of tumours in the F1 mouse was reduced from a control value of 1.71 to 0.96 at the lower dose level and to 0.34 at the higher dose level. From earlier studies done in our laboratory, it appears that mustard oil exerts its effect by inducing the enzymes of drug detoxification and also by changing the profile of the antioxidant defence system. The quantitative and qualitative nature of the active principles and their passage into the F1 progeny remains to be seen.
We report here that the Shigella invasion plasmid antigen (Ipa)B, which is sufficient to induce apoptosis in macrophages, binds to caspase (Casp)-1, but not to Casp-2 or Casp-3. Casp-1 is activated and its specific substrate interleukin-1beta is cleaved shortly after Shigella infection. Macrophages isolated from Casp-1 knock-out mice are not susceptible to Shigella-induced apoptosis, although they respond normally to other apoptotic stimuli. Shigella kills macrophages from casp-3, casp-11, and p53 knock-out mice as well as macrophages overexpressing Bcl-2. We propose that Shigella induces apoptosis by directly activating Casp-1 through IpaB, bypassing signal transduction events and caspases upstream of Casp-1. Taken together these data indicate that Shigella-induced apoptosis is distinct from other forms of apoptosis and seems uniquely dependent on Casp-1.
We recently synthesized a novel cationic amphiphile (N-t-butyl-N'-tetradecyl-3-tetradecylaminopropionamidine or Vectamidine (previously described as diC14-amidine)) that associates with DNA and RNA and facilitates their entry and expression into eukaryotic cells. Among several parameters that have been shown to influence the transfection process, the surface charge density plays a key role. Quantitative information about that charge density associated to the cationic amphiphiles organized in liposomal structure is not yet available. We provide here evidence by titration and microelectrophoresis measurements that an evaluation of the intrinsic acidity constants, the surface pH and the counterion binding constants allows to determine the charge density at physiological pH of Vectamidine liposomes. The knowledge of this superficial charge is a prerequisite to a molecular understanding of the DNA-cationic amphiphile complex formation. The method described could be extended to any kind of cationic amphiphile.
Specular and non-specular X-ray reflectivity intensities of a (Ta/Si)(60) multilayer sample were measured to characterize its interface structure. Since the multilayer has a good reflectance at its multilayer peaks, its performance as a wide-bandpass monochromator for X-ray scattering experiments of polymers has been tested.
Hyperinsulinemia and increased visceral/abdominal fat (VF) are common features of human aging. To examine the relationships among VF, peripheral, and hepatic insulin sensitivity, we studied 4- and 18-mo-old male Sprague-Dawley rats (n = 42) fed ad libitum (4 AL and 18 AL) or moderately calorie restricted (18 CR) up to 18 mo of age. Total fat mass (FM) and VF were decreased in 18 CR to approximately one-third of that of 18 AL (P < 0.001), while lean body mass (LBM) was unchanged. Most important, 18 CR had more FM (65+/-6 vs. 45+/-6 g) but less VF (7.8+/-0.6 vs. 12.3+/-3.3 g) compared with 4 AL (P < 0.01 for both). Thus, the effects of variable VF on HIS could be assessed, independent of FM and age. Marked hepatic insulin resistance ensued with aging (18 AL) and CR restored hepatic insulin sensitivity to the levels of young rats, while peripheral insulin sensitivity remained unchanged (by insulin clamp of 18 mU/kg/min). In fact, the rates of insulin infusion required to maintain basal hepatic glucose production in the presence of pancreatic clamp were 0.75+/-0.10, 1.41+/-0.13, and 0.51+/-0.12 mU/kg . min, in 4 AL, 18 AL, and 18 CR, respectively (P < 0.01 between all groups), and in 18 CR rats infused with insulin at similar rates as in the 18 AL (1.4 mU/kg/min) hepatic glucose production was decreased by 32% (P < 0. 005). Furthermore, when 18 CR rats were fed AL for 14 d, VF rapidly and selectively increased and severe hepatic insulin resistance was induced. We propose that in this animal model the age-associated decrease in hepatic (rather than peripheral) insulin action is the major determinant of fasting hyperinsulinemia and that increased visceral adiposity plays the major role in inducing hepatic insulin resistance. Thus, interventions designed to prevent the accumulation of VF are likely to represent an effective mean to improve carbohydrate metabolism in aging.
The structure of class A beta-lactamases contains an omega-loop associated with the active site, which carries a key catalytic residue, Glu166. A 16-residue omega-loop deletion mutant of beta-lactamase from Staphylococcus aureus PC1, encompassing residues 163-178, was produced in order to examine the functional and structural role of the loop. The crystal structure was determined and refined at 2.3 A, and the kinetics of the mutant enzyme was characterized with a variety of beta-lactam antibiotics. In general, the wild-type beta-lactamase hydrolyzes penicillin compounds better than cephalosporins. In contrast, the deletion of the omega-loop led to a variant enzyme that acts only on cephalosporins, including third generation compounds. Kinetic measurements and electrospray mass spectrometry revealed that the first and third generation cephalosporins form stable acyl-enzyme complexes, except for the chromogenic cephalosporin, nitrocefin, which after acylating the enzyme undergoes hydrolysis at a 1000-fold slower rate than that with wild-type beta-lactamase. Hydrolysis of the acyl-enzyme adducts is prevented because the deletion of the omega-loop eliminates the deacylation apparatus comprising Glu166 and its associated nucleophilic water site. The crystal structure reveals that while the overall fold of the mutant enzyme is similar to that of the native beta-lactamase, local adjustments in the vicinity of the missing loop occurred. The altered beta-lactam specificity is attributed to these structural changes. In the native structure, the omega-loop restricts the conformation of a beta-strand at the edge of the active site depression. Removal of the loop provides the beta-strand with a new degree of conformational flexibility, such that it is displaced inward toward the active site space. Modeled Michaelis complexes with benzylpenicillin and cephaloridine show that the perturbed conformation of the beta-strand is inconsistent with penicillin binding because of steric clashes between the beta-lactam side chain substituent and the beta-strand. In contrast, no clashes occur upon cephalosporin binding. Recognition of third generation cephalosporins is possible because the bulky side chain substituents of the beta-lactam ring typical of these compounds can be accommodated in the space freed by the deletion of the omega-loop.
The allele-specific epigenetic markings of endogenously imprinted genes in placental mammals occur during gametogenesis. The identification of the molecular nature of gametic imprints is the first step towards understanding the mechanistic basis of epigenesis in embryonic and adult somatic tissues. The specific question addressed in this work is whether the closely positioned but oppositely imprinted insulin-like growth factor 2 (IGF 2) and H19 genes, which have similar temporal regulation during development, differ in chromatin structure in mammalian spermatozoa. During terminal differentiation of mammalian spermatozoa, about 3-15% of the haploid genome retains a quasisomatic-type chromatin structure, whereas the remaining genomes interact with protamines that are further cross-linked by-S-S- bridges. Micrococcal nuclease (MNase) and DNase I digestions of human (HSN) and porcine sperm nuclei (PSN) showed that the IGF 2 gene in both types of nuclei retained somatic-type nucleosomes that were close-packed with a periodicity of 150 bp. However, the H19 gene in both species was predominantly organised by unique structural repeats, which were 650-674 bp in PSN and 438-522 bp in HSN, condensing at least 20 kb of chromatin. These results, together with previous studies, suggest that epigenetic chromatin modification leading to preferential condensation of the paternal H19 allele in embryonic tissues is already present in the germ cells.
BACKGROUND: The home care population has high levels of depressive disorder which is unrecognized and untreated. In the UK, social services are charged with a full assessment of need but there appears to be little systematic assessment of depressed mood in their assessment and review procedures. The performance of the SelfCARE(D), a 12-item self-administered depression rating scale, was tested in this population. METHOD: Home care recipients in Lewisham East were invited to complete the SelfCARE(D). Random samples of groups scoring at different levels on the SelfCARE(D) were then interviewed using the GMS/AGECAT system in order to make a standardized psychiatric diagnosis. The sensitivity and specificity, and positive and negative predictive values (PPV and NPV) of the tests were calculated along with the area under ROC curves for different SelfCARE(D) cutpoints and definitions of disorder. RESULTS: 75% of the target population completed the SelfCARE(D). The data suggest that the most efficient cutpoint to use in this population appears to be 7/8, since this gave an NPV of 0.90, a PPV of 0.50 and a yield of 83% of cases of depression. This was achieved with having to complete a second-stage assessment on 17% less of the total population when compared with the 5/6 cutpoint and 9% less than the 6/7 cutpoint. CONCLUSIONS: This study suggests that the SelfCARE(D) may be an acceptable and effective tool for the screening of depression in the home care population. The data presented here support an evaluation of its incorporation into social service assessment and review packages for their elderly home care clients.
OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) express cellular immunity to the purified G1 globular domain of cartilage proteoglycan (PG) aggrecan and whether it is influenced by the removal of keratan sulfate (KS) chains from the molecule. METHODS: The G1 globular domain of PG was purified from mature bovine articular cartilage, digested with keratanase, and used in proliferation assays with peripheral blood lymphocytes (PBL) isolated from 43 patients with RA, 11 patients with nonarticular rheumatism (NAR), including soft tissue rheumatism and mechanical back pain, and 13 healthy age- and sex-matched control subjects. RESULTS: Removal of KS chains from the G1 globular domain resulted in significantly increased prevalence and values of cellular immune responses to G1 in RA patients compared with the control and NAR groups. In the majority of RA patients, KS chains on G1 significantly inhibited its immune recognition by PBL. There was no significant effect of KS removal on the immunity to G1 in patients with NAR and in the healthy control group. CONCLUSION: These results reveal that immune reactivity to the G1 globular domain of the cartilage PG aggrecan is enhanced in patients with RA but only when KS chains are removed. Thus, KS chains inhibit immune responses to this domain of aggrecan. Since immunity to the G1 globular domain of aggrecan induces an erosive polyarthritis in BALB/c mice after removal of KS chains, immunity to the G1 globular domain, cleaved by proteases to remove KS chains, may play a role in the pathogenesis of RA.
The positive-strand transcripts as well as negative-strand transcripts of mouse hepatitis virus (MHV) defective interfering (DI) RNA, when introduced into MHV-infected cells, resulted in DI RNA replication and accumulation. The leader sequence of the majority of DI RNAs that accumulated from the expression of negative-strand DI RNA transcripts with no extra non-MHV nucleotides at the 3' end switched to that of helper virus, whereas this leader sequence switching did not occur in most of the positive-strand DI RNAs that accumulated from the expressed negative-strand DI RNA transcripts with extra non-MHV nucleotides at the 3' end. These data demonstrated that the extra 4 nucleotides at the 3'-end of negative-strand DI RNA transcripts affected leader sequence switching on DI RNA, and indicated that the leader switching probably occurred during positive-strand DI RNA synthesis.
OBJECTIVE: To identify risk factors for polymicrobial bloodstream infections (BSIs) in neonatal intensive care unit (NICU) patients during an outbreak of BSIs. DESIGN: During an outbreak of BSIs, we conducted a retrospective cohort study, assessed NICU infection control practices and patient exposure to NICU healthcare workers (HCWs), and obtained cultures of the environment and HCW hands. PATIENTS: During the period May 3 to 7, 1996, 5 infants contracted BSIs caused by both Enterobacter cloacae and Pseudomonas aeruginosa, and one infant contracted a BSI caused by E cloacae only. For each pathogen, all isolates were identical on DNA typing. RESULTS: Infants exposed to the following were more likely than nonexposed infants to have BSI: umbilical venous catheters (6/14 vs 0/7, P = .05), total parenteral nutrition given simultaneously with a dextrose/electrolyte solution (6/12 vs 0/9, P = .02), or one HCW (5/7 vs 1/13, P = .007). Neither environmental nor HCW hand cultures yielded the outbreak pathogens. Quality control cultures of intravenous solution bags were negative. CONCLUSIONS: We speculate that a dextrose multidose vial became contaminated during manipulation or needle puncture and that successive use of this contaminated vial for multiple patients may have been responsible for BSIs. Aseptic techniques must be employed when multidose vial medications are used. Single-dose vials should be used for parenteral additives whenever possible to reduce the risk of extrinsic contamination and subsequent transmission of nosocomial pathogens.
BACKGROUND: The 1994 Centers for Disease Control and Prevention draft Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities did not exempt pediatric facilities from instituting controls to prevent nosocomial tuberculosis (TB) transmission. Many researchers contend that TB disease in children does not require such rigid controls. We surveyed acute-care pediatric facilities in the United States to determine adherence to patient and family isolation policies and procedures. METHODS: The study included 4 mailings of a survey to infection control professionals at 284 US children's hospitals and adult acute-care hospitals with > 30 pediatric beds. RESULTS: The overall response rate was 69%. Only 41% of respondents reported having a written TB policy specifically designed for pediatric patients. Whereas 98% of respondents isolated pediatric patients with confirmed pulmonary TB, only 69% reported isolation of patients with miliary TB, and 79% reported isolation of patients with positive gastric aspirates. TB isolation policies for adult visitors were in place at 69% of hospitals, and 50% of hospitals evaluated adults for TB as part of the child's TB treatment plan. A median of 3 contact investigations occurred at each of 47% of respondent hospitals in the preceding 5 years. CONCLUSIONS: Isolation and infection control policies for children with pulmonary TB largely conformed to published guidelines but varied for children with nonpulmonary TB. Because the greatest risk of nosocomial TB transmission in pediatric facilities comes from adults with TB, a rapid TB screening process for parents and adult contacts accompanying affected children should be instituted at facilities caring for children.
BACKGROUND: The 1994 Centers for Disease Control and Prevention draft Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities did not exempt pediatric facilities from instituting controls to prevent nosocomial tuberculosis (TB) transmission. Many researchers contend that TB disease in children does not require such rigid controls. We surveyed acute-care pediatric facilities in the United States to determine adherence to environmental and administrative control recommendations. METHODS: The study included 4 mailings of a survey to infection control professionals at 284 US children's hospitals and adult acute-care hospitals with > 30 pediatric beds. RESULTS: Isolation rooms (IRs) generally conformed to recommended guidelines; 92% of respondents reported IRs with > or = 6 air changes per hour, 90% reported 1-pass air and negative pressure, and 89% reported that IRs were private rooms. A sufficient number of inpatient IRs were reported by 88%, but only 42% had IRs in outpatient areas, and 19% had IRs in off-site clinics. Employee tuberculin skin-test programs were in place at 98% of facilities, but policies pertaining to implementation varied. Employees' use of personal respirators increased at respondent hospitals from 1991 to 1994, but as late as 1994, nearly one third still used surgical masks for high-risk procedures. CONCLUSIONS: Environmental and administrative controls used by respondent hospitals largely conformed to published guidelines. Because definitive studies that quantify the risk of nosocomial M tuberculosis transmission in pediatric settings have yet to be performed, pediatric facilities are required to have the same protections in place as do their adult counterparts.
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PURPOSE: To evaluate the appropriateness of triage decisions in a busy ophthalmic casualty department and to assess the diagnostic and management skills of eye-dedicated nurse practitioners. METHODS: Three hundred and one consecutive patients attending the Birmingham and Midland Eye Centre (BMEC) accident and emergency (A&E) department over a 2 week period were included in this prospective study. Patients were categorised in terms of urgency in concordance with strict guidelines, and the agreement between the final diagnosis and this system of prioritisation was then investigated. To evaluate nurse practitioner (NP) skills, all patients seen and managed by a NP were also assessed by the most senior doctor in casualty at the time in a masked fashion. Waiting times and a breakdown of waiting times were also calculated. RESULTS: Upon establishment of a diagnosis, triage category allocation was found to be appropriate in all 301 cases. Fifty patients (16.67%) were seen by the NP. Of these the supervising doctor concurred with the NP diagnosis in all cases and with the proposed management in 96% of cases. The mean waiting time (+/- SD) was 83.43 +/- 45.84 min, with a range of 5-335 min. The delay before being attended to was greater for less urgent cases as categorised by the triage system. CONCLUSION: This study confirms the high standard of diagnostic and management skills of the ophthalmic NP and indicates that the triage system of patient prioritisation is accurate. Waiting times in the A&E department remain unacceptable and ways of addressing this include improved ophthalmic training of general practitioners, diverting a greater proportion of non-acute cases to the primary care clinic and expanding the role of the NP.
Insulin resistance and increased fat mass (FM) are common in human aging. We aimed to investigate the relationship between the age-dependent increase in FM and insulin resistance (by euglycemic hyperinsulinemic clamp technique), in a homogenous rodent model. The decline in insulin responsiveness was linear until late adulthood when body weight, FM, and epididymal fat reached a critical amount (r > .750, for all). Above this critical point, there was no further decline in insulin responsiveness with aging and with increased BW (p < .00001 for all spline curve analyses). This decline in insulin-mediated glucose uptake was accounted for by a decrease in whole body glycolytic rate with no change in the rate of glycogen synthesis. Thus, in this homogenous model, an early increase in FM is associated with impairment in insulin action until a critical FM is achieved, after which there is no additional insulin resistance with aging. We suggest that decreasing insulin responsiveness, in a heterogeneous group such as humans, will only occur within a specific accretion of visceral or total FM.
Unlike other somatic cells, human placental trophoblast cells do not express the highly polymorphic HLA-A and HLA-B human leukocyte major histocompatibility antigens that would stimulate maternal immunological rejection of the fetus. To investigate mechanisms underlying cell lineage-specific expression, cell lines were generated from homozygous matings of HLA-B27 transgenic mice. Trophoblast cell lines were generated from gestation day 10 placentas and fibroblasts were cultured from gestation day 13/14 embryos. Polymerase chain reaction (PCR) readily identified HLA-B DNA in transgenic trophoblastic cells but specific mRNA was of low abundance, being detectable by reverse transcriptase PCR but not by Northern blot hybridization. HLA-B-specific protein in/on the trophoblast cells was undetectable by cell enzyme-linked immunosorbent assay and the protein was not induced by exposing the trophoblastic cells to interferon-gamma (IFN-gamma). Restricted expression was specific for the HLA-B transgene and its antigen; IFN-gamma-inducible endogenous H-2Db class I antigens were detectable on the trophoblast cells. In contrast to the trophoblastic cells, HLA-B27 transgenic fibroblasts expressed IFN-gamma-inducible HLA class I antigens as well as H-2Db antigens. Thus, the mechanism(s) regulating expression of the polymorphic HLA-B antigen in trophoblastic cells is gene-specific, IFN-gamma-resistant and operative at the level of transcription or immediate post-transcription.