Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice.
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Biomedical subjects
Publications and source records attributed to A Tewari.
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An epidemiological study on interrelationship between dental caries and sugar consumption conducted on 1265 children in the age of 5-15 years revealed a positive association of dental caries experience with total sugar exposures, between meal sugar exposures and at meal sugar exposures. As the total increased from 3 to 4 in a day, a corresponding jump of 1 deft+DMFT and 2 defs+DMFS was noted, which was clinically and statistically significant. It was deduced that total sugar exposures per day should be limited to 3, out of which two should be at meal time and one between meals.
This study is a part of a larger preventive oral health feasibility module embarked on a population of 120,000 of Raipurrani, district Ambala (Haryana). The KAP analysis of about 2000 individuals (including school children) on cross-sectional basis at baseline, one and two years after the implementation of knowledge about oral health measures to the community utilizing the existing health infrastructure at CHC, the Anganwadi workers (ICDS Scheme) and through school teachers in the schools revealed that at baseline datun was the most prevalent (63%) oral hygiene measure used in the community and students. After implementation, the practice of brushing thrice, twice and once daily increased but the most prevalent frequency remained once a day (39% out of 66 percent using brush in community and 37% out of 76 percent in students after 2 and 11/2 years of implementation respectively) followed by twice a day (23 & 31% respectively). A similar pattern of frequency was observed about datun users also, though the number using datun substantially declined from 62% to 33% in community and 63 to 23% in students after implementation.
The monoclonal antibody (mAb) 1801 has been reported to identify an N-terminal determinant within the tumor-suppressor protein p53 located between amino acids 32 and 79. This region contains two potential sites for serine phosphorylation at amino acids 33 and 46. Using a novel technique which dephosphorylates proteins in situ in fixed permeabilized cells, we have unmasked determinants in p53 recognized by mAb 1801, allowing additional sites of p53 protein to be detected in immunohistochemically reacted cells. This result indicates that phosphorylation at one or both sites within the determinant recognized by mAb 1801 previously blocked antibody-ligand interaction. It further suggests that in situ dephosphorylation may be of more general use in identifying antibodies which can only bind to epitopes in a particular phosphorylation state.
The efficacy of purified cross-linked human hemoglobin solution in maintaining the metabolic integrity of perfused livers from fed rats was determined and compared with that of livers recirculated with red blood cells, perfluorocarbon, and Krebs' Ringer bicarbonate buffer media at normal and accelerated flow rates. The data indicate that oxygen utilization was comparable in livers perfused with red blood cell medium (53.5 +/- 4.0 microL.g liver-1.min-1), hemoglobin (45.7 +/- 1.9), and perfluorocarbon (57.2 +/- 6.1) and less in livers perfused with Krebs' Ringer bicarbonate buffer solution at normal (17.4 +/- 1.4) and high (27.7 +/- 1.4) flow rates. Bile flow, the outflow of glucose and lactic acid, and residual glycogen levels were similar when livers were perfused with red blood cells (hematocrit, 19) and hemoglobin solutions containing 7 g hemoglobin/dL at flow rates of 1.1-1.2 mL.g liver-1.min-1. However, livers perfused with perfluorocarbon at 1.1 mL.g-1.min-1 showed a significantly greater (P less than 0.01) decline in bile flow and outflow of glucose and lactic acid. Livers perfused with Krebs' Ringer bicarbonate buffer at normal (1.3 mL.g-1.min-1) and accelerated flow rates (3.0 mL.g-1.min-1) also showed a progressive decrease in bile flow and marked glycogenolysis as well as depletion of adenosine triphosphate content. In addition, morphological studies (light and electron microscopy) showed more vacuoles, membrane alterations, and increased mitochondrial swelling in livers perfused with Krebs' Ringer bicarbonate buffer and perfluorocarbon. These findings suggest that hepatocyte function in livers from fed rats is maintained equally well with hemoglobin solutions and with red blood cell medium, suggesting that cross-linked hemoglobin solution may serve as an effective blood substitute for maintaining adequate oxygenation and metabolic integrity of the isolated perfused rat liver.
Among air pollutants, sulfur dioxide has been found to be very injurious. The present article deals with the adverse effects of sulfur dioxide gas on metals, metal alloys, buildings and plants, animals and human beings.
The biological oxygen demand (B.O.D.) is an important parameter for the measurement of organic pollutants in waste water. The present paper deals with the various causes which may be responsible for B.O.D. variations in waste water of different types of industrial effluents.
The KAP survey on oral health practices of 3247 individuals, 6-60 years of age, of Sidhaura block of Haryana revealed that use of dattan was more prevalent (56% in adult community & 49% students) than tooth brush (35% adult community & 34% students). 37% of the total community had the knowledge of brush being the best oral hygiene measure. 25% of the community using brush were brushing only once/day. The knowledge of the community regarding the role of fluorides in prevention of dental caries was completely lacking: 1.8% of the community was using fluoride dentifrice. 35-45 percent of the community were practising sweet foods/drinks etc. four times a day. The snyder test showed a positive relation with frequency of sugar intake.
Fifty repaired complete cleft lip and palate cases (38 UCLP and 12 BCLP) in the age range of 6 to 14 years were evaluated for transverse and vertical asymmetry using postero-anterior cephalograms. A total of nine bilateral landmarks, representing upper face, mid face and lower face were used. Results showed that asymmetry was not confined to any single plane of reference but manifested in both dimensions--transverse and vertical. The UCLP group had greater asymmetry of mid face than the BCLP group. Asymmetry was found to be extending to distant areas besides the contiguous structures.
Plasma renin activity was measured in ten diabetics with nephropathy, 10 uncomplicated diabetics and 10 normal healthy controls. All the groups were comparable for age, sex, and duration of diabetes. Plasma renin activity was found to be significantly lower in patients with nephropathy in comparison to uncomplicated diabetics and normal healthy controls. There was no correlation between plasma renin activity and mean blood pressure or degrees of renal failure. These findings raise the possibility that microangiopathic changes occurring in the glomeruli and juxta-glomerular apparatus may alter the renin-angiotensin system. Also the finding of low renin in diabetics with nephropathy may modify management policies.
Dental caries was recorded using WHO index (1983) and Moller's index (1966) in 1265 children in the age group of 5, 8, 11 and 15 years to determine the conversion and correlation figures, so as to facilitate cross comparison and quick appraisal where either of the systems have been used in epidemiological studies. The results revealed that dental caries was recorded higher with Moller's index as compared to the WHO index; on an average the difference was fourteen percent in point prevalence, one deft + DMFT and one and a half defs + DMFS.
Forty cleft cases in the age range of 5-12 years where the palatal repair had been performed at 16-24 months (17 cases), 24-36 months (15 cases) and 36-72 months (8 cases) were assessed retrospectively, for the status of maxillary arch and were segregated as acceptable and unacceptable. Plaster casts were prepared from alginate impressions and their graphical reproduction using Huddart's technique, were used to measure the alveolar arch. Anterior palatal measurement (C-C') and posterior palatal measurement (P-P') of the cleft subjects were compared with that in the non-cleft matched controls. The 16-24 month group showed 41.2% acceptable and 58.8% unacceptable arch cases. The 24-36 month group showed that 73.4% had acceptable arches and 26.6% had unacceptable arches. In the 36-72 months group the arch was acceptable in 62.5% cases and unacceptable in 37.5% cases. It was concluded that palatal repair performed before 24 months of age adversely affected the maxillary growth, whereas most favourable growth of maxillary arch occurred when the repair was done between 24-36 months.
Cariogenic potential of a few children's favourite snacks, assessed by evaluation of pH modulations on their respective consumption after 2,5,10,20,30 and 40 minutes compared to 10 percent sucrose control using pooled plaque method, in 8-12 years old children revealed lollipop (hard sucking candy) to be the most cariogenic and samosa without chutney to be the least cariogenic. The cariogenic potential of ice creams were similar, however, low as compared to sucrose solution of 10 percent.
The study was conducted on 1251 6-12-year-old children, to evaluate the effect of topical application of NaF, APF and Duraphat given at six monthly interval assessed after 2.1/2 years revealed the percentage caries reduction with sodium fluoride to be in the range of 20-24 percent on base line teeth and 30-33 percent on teeth erupted during study, showing more effect on newly erupted teeth. In APF group, the caries reduction was 32-37 percent, in the DMFT and DMFS-slightly more on teeth erupted during study than on baseline teeth. The dental caries reduction with Duraphat (NaF varnish) was in the range of 70-75 percent-slightly more on newly erupted teeth. Equally high degree of efficacy was also noted on occlusal surfaces. Duraphat showed the greatest public health potential.
Potentially fatal physiologic and metabolic derangements can occur in response to bacterial infection in animals and man. Recently it has been shown that alterations in the levels of circulating cytokines such as IL-6 and TNF-alpha occur shortly after bacterial challenge. To understand better the role of IL-6 in inflammation, we investigated the effects of in vivo anti-mouse IL-6 antibody treatment in a mouse model of septic shock. Rat anti-mouse IL-6 neutralizing mAb was produced from splenocytes of an animal immunized with mouse rIL-6. This mAb, MP5-20F3, was a very potent and specific antagonist of mouse IL-6 in vitro bioactivity, demonstrated using the NFS60 myelomonocytic and KD83 plasmacytoma target cell lines, and also immunoprecipitated radiolabeled IL-6. Anti-IL-6 mAb pretreatment of mice subsequently challenged with lethal doses of i.p. Escherichia coli or i.v. TNF-alpha protected mice from death caused by these treatments. Pretreatment of E. coli-challenged mice with anti-IL-6 led to an increase in serum TNF bioactivity, in comparison to isotype control antibody, implicating IL-6 as a negative modulator of TNF in vivo. Anti-TNF-alpha treatment of mice challenged i.p. with live E. coli resulted in a 70% decrease in serum IL-6 levels, determined by immunoenzymetric assay, compared to control antibody, thereby supporting a role for TNF-alpha as a positive regulator of IL-6 levels. We conclude that IL-6 is a mediator in lethal E. coli infection, and suggest that antagonists of IL-6 may be beneficial therapeutically in life-threatening bacterial infection.
Recombinant human interleukin-1 beta was given in 5 daily intravenous infusions to ten patients with metastatic malignant disorders as part of an antineoplastic trial. All ten patients experienced transient increases in heart rate, low-grade fevers, and rigors. A neutrophil-dominated 100% rise in leucocyte counts occurred 4-8 h after treatment. Leucocyte counts returned to baseline levels within 24 h of interleukin-1 beta infusion. A 50% rise in platelets occurred in response to interleukin-1 beta; the increase in platelet counts was first noted 6 days after treatment began and was sustained for 24 days after treatment. Interleukin-1 beta may therefore be beneficial in the treatment of conditions of thrombocytopenia associated with haematological disorders and chemotherapy for malignant disorders.
The X gene product of human hepatitis B virus (HBV) trans-activates the HBV enhancer. In order to identify domains responsive to trans-activation by the X gene, we introduced a series of mutations into the HBV enhancer and assayed the enhancer activities in the presence of the X gene product. Our results suggest that the EP domain of the enhancer is essential for trans-activation by the X gene.