The ultimate panacea--relief of pain.
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Humans↗
Biomedical subjects
S K Ray
Publications and source records attributed to S K Ray.
A comparative study of immunisation status of children in West Bengal.
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Humans↗
"Resultant bond moment" as a newly developed electronic parameter in the design of antibacterial, antiprotozoal nitroimidazole derivatives.
Nineteen nitroimidazole derivatives have been reported to be effective antibacterial against one strain each of Bacteroides fragilis and Clostridium perfringens. The negative logarithms of minimum inhibitory concentrations (MICs) of these nitroimidazoles were fitted by a biostatistical relation involving a newly designed structural descriptor, the Resultant Bond Moment (RBM). RBM was developed on the basis of the chemical attribute of bond moments of heteroatoms. RBM reflects the electronic characteristic of the molecule. Apart from this, steric, electronic, and hydrophobic parameters were also utilised in the search of a best fit regression equation. On the basis of these equations new investigative nitroimidazole derivatives have been predicted concerning their antibacterial and antiprotozoal efficacy.
Anti-Bacterial Agents↗
A report of diphtheria surveillance from a rural medical college hospital.
A 5-year sentinel surveillance of diphtheria from 1989 to 1993 was undertaken at a rural medical college hospital. No significant change in the number of diphtheria cases was observed in spite of sustained high level of diphtheria, pertussis, tetanus vaccine-3 doses (DPT3) coverage. Most of the diphtheria cases occurred during July to November. Age distribution of diphtheria cases showed that more than 75% occurred above 2 years age (except in 1989) and around 65% cases above 3 years age. The age shift in diphtheria signified success of primary diphtheria immunisation, as well as indicated the lack of coverage with booster doses at appropriate ages. Because of high coverage with primary diphtheria immunisation there was decrease in circulating toxigenic C diphtheriae resulting in less natural boosting of antibody titre. Thus, in absence of booster immunisation, the older children and adults were more vulnerable to diphtheria. The findings of the study justified the need of emphasising importance of booster diphtheria immunisation at appropriate ages for effective control of diphtheria.
Adult↗
Prevalence of canine demodicosis in Orissa (India).
Examination of the records of 12 hospitals from the five districts of Orissa showed that 50,987 dogs were presented for treatment during the period of 5 years covering 1987-1988 to 1991-1992. Demodicosis was detected in 1697 (3%) cases. There was no difference in the occurrence of the disease in male (51%) and female (49%) dogs. The disease was recorded in 60%, 23% and 17% of dogs up to 1 year, 1-2 years and above 2 years of age respectively, suggesting that young dogs up to 1 year of age are more susceptible. Further study revealed that Tibetan apso are more susceptible (47%) than Doberman (23%), Alsatian (18%) and mongrels (12%). A total of 912 dogs with natural dermatitis were examined during the 5-year period and 35% of the dogs were found to have demodicosis. Out of these, 208 dogs (65%) had localised lesions and 111 (35%) had generalised lesions. The study revealed that dogs up to 1 year of age are more frequently affected (60%) than dogs of 1-2 years (23%) and above 2 years of age (17%). There was no difference between the susceptibility of male (49%) and female (51%) dogs. The prevalence was high in Tibetan apso (41%) as compared to Doberman (26%), Alsatian (16%) and mongrels (17%).
Age Factors↗
Transcriptional activation of fibroblast growth factor 1.B promoter is mediated through an 18-base pair cis-acting element.
Four different transcripts encoding fibroblast growth factor 1 (FGF-1, also known as aFGF) have been previously identified in our laboratory. Among them, FGF-1.B is the major transcript expressed specifically in the neuronal cells in brain tissue. Using the transient transfection experiment in a glioblastoma cell line, U1240MG, that expresses 1.B, we previously identified two regulatory regions (RR1 and RR2) in the brain-specific promoter, FGF-1.B. In the present study, we showed that the minimal region required for the DNA-protein interaction in RR2 resides in an 18-base pair (-484 to -467) sequence, by using DNase I footprinting and methylation interference studies and electrophoretic mobility shift assays. This minimal cis-acting element was found to be sufficient in enhancing the reporter activity driven by the heterologous herpes simplex virus thymidine kinase promoter in the 1.B-positive U1240MG cell line. This enhancing effect, however, was not detected in a glioblastoma cell line, U1242MG, which is negative for 1.B expression. By electrophoretic mobility shift assays, we also identified a specific DNA-protein complex, namely complex I, which is specific for 1.B-positive cell lines and human brain tissue. By in situ UV cross-linking experiment, we further showed that complex I contains two major DNA-binding proteins of apparent molecular masses of 37 and 98 kDa. Our results suggest that the formation of complex I, resulting from the heterodimerization of a 37-kDa protein (1.B-specific) and a 98-kDa protein (ubiquitous) may likely be a prerequisite for the enhanced expression of 1.B transcript in neuronal cells.
DNA↗
Studies on 'zinc deficiency syndrome' in black bengal goats (Capra hircus) fed with fodder (Andropogon gayanus) grown on soil treated with an excess of calcium and phosphorus fertilizer.
Overliming and excessive application of superphosphate caused a zinc deficiency in the soil and so reduced the uptake of zinc by fodder plants. Bucks reared on such fodder had significantly (p < 0.01) less zinc in their hair compared with controls and suffered from 'conditioned zinc deficiency syndrome' with a significant (p < 0.01) loss of body weight, stunted growth, alopecia, lethargy, abnormal (kyphotic) gait, anorexia, digestive and respiratory problems. Oral supplementation with zinc sulphate very rapidly improved these conditions to near normality. Histological examination of samples of skin and testis from the zinc-deficient bucks revealed formation of excessive keratin, retention of nuclei in the stratum corneum and reduction in the width of the stratum granulosum in the skin, while samples of testis indicated degenerative changes, including atrophy of the seminiferous tubules, hyperplasia of the germinal epithelium and thickening of the walls of blood vessels.
Alopecia↗
Amphibian FGF-1 is structurally and functionally similar to but antigenically distinguishable from its mammalian counterpart.
Recent studies have shown that fibroblast growth factors (FGF) play an important role in the diverse cellular mechanisms involved with vertebrate development. One system which has received a great deal of attention is the developing limb in part because of the extensive epithelial-mesenchymal interactions that take place during this process. Because it closely parallels the developmental process of the limb and is a model for wound repair, the phenomenon of amphibian limb regeneration has been used to investigate the role of FGF in these processes. We have recently reported on the cloning and functional characterization of an FGF receptor (FGFR) isolated from amphibian regenerative tissue. In this report, we describe the isolation and characterization of an FGF-1 molecule from the newt, Notophthalmus viridescens. Amino acid sequence comparisons indicate that the newt FGF-1 exhibits between 79 to 83% identity with FGF-1 from mammalian and avian species. The full length cDNA of the newt FGF-1 was cloned into a prokaryotic expression vector and purified from E. coli. Although the newt FGF-1 shares a high degree of primary amino acid sequence similarity with other FGF-1 molecules, the recombinant protein was not detected in a Western blot analysis using a polyclonal antibody directed against mammalian FGF-1. Despite the antigenic divergence, the newt FGF-1 was capable of binding to NIH/3T3 and Chinese hamster ovary cells overexpressing mammalian and amphibian FGFRs with dissociation constants comparable to those reported for mammalian FGF-1. Newt FGF-1 could also be cross-linked to receptors on the surface of NIH/3T3 cells. In addition, it elicits a mitogenic response in NIH/3T3 cells indistinguishable from human recombinant FGF-1.
3T3 Cells↗
Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease.
The immune system's ability to distinguish self and nonself is essential for both host defense against foreign agents and protection of self-antigens from autoimmune destruction. Such discrimination is complicated by extensive structural homology shared between foreign and self antigens. One hypothesis to explain the development of an autoimmune response is that some B cells activated by foreign antigen acquire, through somatic mutation, specificity for both the eliciting foreign antigen and self antigen. If such clones arise frequently, there must be a mechanism for their elimination. We have analyzed the extent of autoreactivity arising in a nonautoimmune host during the response to a foreign antigen. To overcome the process of apoptosis in primary B cells that might routinely eliminate autoreactive clones, we generated B-cell hybridomas from spleen cells of immunized mice by using a fusion partner constitutively expressing bcl-2. Multiple lines were obtained that recognize simultaneously the hapten phosphorylcholine and the self antigen double-stranded DNA. This dual specificity was not present early but was detected by day 10 after immunization. Some of these cross-reactive antibodies deposit in kidneys in a pattern similar to what is seen in autoimmune disease. These results demonstrate that autoantibodies arise at a high frequency as part of a response to foreign antigen. It has previously been shown that autoreactivity is regulated by central deletion; these data demonstrate a need for negative selection in peripheral lymphoid organs also, to regulate autoantibodies acquiring their self-specificity by somatic mutation.
Animals↗
Functional characterization of the brain-specific FGF-1 promoter, FGF-1.B.
Expression of alternatively spliced human FGF-1 (or aFGF) transcripts is regulated in a tissue-specific manner via multiple promoters. To identify the cis-regulatory elements in the brain-specific FGF-1.B promoter, we constructed a series of promoter deletions fused to the luciferase reporter gene and transfected into an FGF-1.B positive glioblastoma cell line, U1240MG, and a 1.B negative cell line, U1242MG. Results of transient transfections indicate three elements that are involved in the positive regulation of FGF-1.B expression. The core promoter is located in a 40-base pair region (between -92 and -49), and two regulatory regions (RR-1 and RR-2) are located within the 540-base pair region 5' to the major transcription start site (defined as +1). Electrophoretic mobility shift assays and footprinting analysis have identified sequence-specific binding sites in RR-1 and RR-2. Mutants of RR-2 abolished binding to nuclear proteins and showed diminished luciferase reporter activity. The effects seen are specific for the U1240MG cell line, supporting a role for RR-2 in the tissue-specific regulation of FGF-1.B. Southwestern analysis using an oligonucleotide probe derived from RR-2 (nucleotides -489 to -467) further identified a 37-kDa protein that is present in nuclear extracts from U1240MG and brain but not from U1242MG.
Base Sequence↗
Potentiation of antiproliferative effects of monoclonal antibody Lym-1 and immunoconjugate Lym-1-gelonin on human Burkitt's lymphoma cells with gamma-interferon and tumor necrosis factor.
A type I ribosome inactivating protein, gelonin, was linked to Lym-1, a murine monoclonal antibody reactive with a polymorphic determinant of class II HLA-DR histocompatibility leukocyte antigen (HLA) on human lymphoma cells, via a disulfide linkage using the heterobifunctional cross-linking agent, N-succinimidyl-3-(2-pyridyldithio) propionate. This immunotoxin was purified from unreacted gelonin and unconjugated Lym-1 by fast protein liquid chromatography using sephacryl S-300 gel filtration and blue sepharose affinity gradient separation. Binding of Lym-1-gelonin immunoconjugate to human Raji Burkitt's lymphoma cells was demonstrated by indirect immunofluorescence using flow cytometry. Lym-1-gelonin was very active in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium salt and sulforhodamine B in vitro cytotoxicity assays against the Raji lymphoma cell line and confirmed the fact that monoclonal antibody Lym-1 internalizes into human lymphoma cells. A weaker cytostatic antiproliferative effect was also noted for unconjugated Lym-1. gamma-interferon augmented the antiproliferative effects of Lym-1-gelonin conjugate and unconjugated Lym-1, by having a direct cytotoxic effect on the Raji cells. Tumor necrosis factor-alpha also enhanced the antiproliferative effect of unconjugated Lym-1, but did not significantly augment the cytotoxic activity of the Lym-1-gelonin conjugate. These results suggest that anti-HLA class II monoclonal antibodies may be useful in constructing immunotoxins for the treatment of human lymphomas and leukemias expressing HLA class II antigens, and that unconjugated anti-HLA class II monoclonal antibodies may be therapeutically useful in conjunction with recombinant cytokines, especially gamma-interferon.
Animals↗
Determination of differential scatter-air ratios (dSAR) for three-dimensional scatter integration.
Scatter dose may be calculated by summing the scatter contribution from individual volume elements. These contributions may be represented by differential scatter-air ratios (dSAR). Determination of dSAR from measured data is only approximately correct for second and higher orders of scatter and yields values often limited to one significant figure. Monte Carlo calculation, on the other hand, is time intensive, requires some knowledge of the beam's x-ray spectrum, and mastering the complexities of a program such as EGS4. Total scatter dose at a point may be determined by measuring depth dose or tissue-air ratios and partitioning the dose into its primary and scatter components. Scatter may be represented by scatter-air ratios, which can be characterized by the sum of first, second, and higher orders of scatter. The first scatter dose may be computed exactly by summing the first scatter contribution from individual elements, determined from the first principle. Separation of dSAR into primary attenuation and depth-independent terms allows the latter to be precomputed once for a given energy and stored in tabular form. Second scatter may be treated in a similar manner. The higher orders of scatter are computed by subtracting the sum of calculated first and second scatter doses from the total scatter dose. Elements close to and approximately 1 cm above the point of calculation contribute most heavily to the first scatter dose. Compared to the first scatter dose, the second scatter dose contribution is lower, particularly for elements close to the point of calculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Humans↗
Clinical use of a concomitant boost technique using a gypsum compensator.
PURPOSE: To develop a clinical procedure to treat field within a field (concomitant boost) portals with a single compensated field. METHODS AND MATERIALS: An ordinary manual cerrobend block former was used to produce styrofoam molds from simulator film data. A special gypsum compound was poured into the molds. The compensator block is independently mounted to the treatment machine via a custom-made compensator holder. RESULTS: Measurements confirm that the inhomogeneous dose distribution has been reliably delivered via this technique. The accuracy of placement of the high dose region is sufficient for clinical use. CONCLUSION: The procedure enables the concomitant boost effect to be easily implemented in the clinic without increasing clinical setup time.
Calcium Sulfate↗
The utility of SPECT lung perfusion scans in minimizing and assessing the physiologic consequences of thoracic irradiation.
PURPOSE: Three-dimensional single photon emission computed tomography lung perfusion scans (SPECT) provide a unique quantitative 3-dimensional map of the distribution of functioning pulmonary vascular/alveolar subunits, information not provided by other imaging modalities. This report describes our initial experience utilizing these scans to assist in the design of radiation treatment beams and to assess changes in regional lung function following irradiation. METHODS AND MATERIALS: Patients were immobilized and scanned in the treatment position with appropriate fiducial markers. Four millicuries of technetium 99M microaggregated albumin were injected and SPECT images of the lung were generated. Pre-treatment SPECT images were used to help design radiation beams to minimize irradiation of functioning lung. Pre- and post-treatment scans were compared to assess changes in regional function. These changes in function were then correlated with the regional radiation dose. RESULTS: Pre-radiotherapy SPECT scans were obtained in 18 patients (11 with lung cancer). Marked variations in regional function were frequently noted. In patients with primary lung tumors, these variations were not necessarily immediately adjacent to the tumor volume. In general, patients with poor pulmonary function pre-treatment, in whom one would like to spare as much normal lung as possible, had the most non-uniform distribution throughout the lung of functioning vascular/alveolar subunits. In these cases, pre-treatment scans were most useful in designing radiation portals to minimize irradiation of functioning lung. SPECT scans were also used to detect changes in regional lung function secondary to radiotherapy in four patients. With doses in excess of 40 Gy, reductions in regional function were noted 1-6 months following completion of radiotherapy. These reductions were not necessarily accompanied by reductions in conventional pulmonary function tests, which are assessments of whole lung function and may not reflect regional lung injury if the volume affected is small. CONCLUSIONS: SPECT lung scans provide an excellent means of assessing regional lung function, superior to that obtainable with planar images. The functional data provided by the SPECT images is useful in designing "optimal" radiation treatment beams and in assessing the effect of radiotherapy on regional lung functions. Efforts are continuing in our laboratory to develop a dose response curve for regional lung damage using the tools of SPECT scanning and 3-dimensional dose calculations.
Aged↗
3-dimensional optimization of multiple arcs for stereotactic radiosurgery.
PURPOSE: During linear accelerator-based radiosurgery, the physicians and physicists need to determine which combination of treatment arcs are "best" with regard to target coverage and incidental dose to adjacent structures. This is a complex problem, especially when targets are geometrically close to critical structures. The purpose of this article is to present a method to mathematically determine a set of arcs to produce desired target and normal structure dose distributions in linear accelerator radiosurgery. METHODS AND MATERIALS: Nonlinear least squares regression was used to determine the table angles and gantry angle arc ranges and their associated beam weights appropriate to linear accelerator radiosurgery. RESULTS: Three cases are presented: (a) critical structure close to target volume; (b) target volume too large for the largest collimator to cover the volume with one isocenter and a standard plan; (c) target volume located within one critical structure and close to another critical structure. The optimized treatment plans are all shown to be superior to a defined standard plan. CONCLUSION: The method successfully enables one to determine nonstandard arcs which achieve the desired results. In particular, the method enables one to find clinical treatment solutions, even when the desired results cannot be a priori defined.
Humans↗
Utilization of maternal services in west Bengal.
A study was conducted in selected blocks of West Bengal to assess the utilization of available maternal health services specially immunization, antenatal care and other services. Coverage with two doses of tetanus toxoid levels varied between 58.6 to 86.7% but it fell far short of Universal Immunization Programme target of 100%. Drop out rates were slightly higher in the rural areas. It was observed that in 5 out of 7 blocks more than 55% of the deliveries were conducted either at hospital or Primary Health Centre by health personnel. However, untrained dais predominated over the trained dais in conducting deliveries in most of the areas. This indicates the poor availability or utilization of the latter.
Female↗
Identification of a 60-kilodalton Rb-binding protein, RBP60, that allows the Rb-E2F complex to bind DNA.
Several reports have indicated that the product of the retinoblastoma gene (Rb) complexes with the transcription factor E2F. We present evidence that the DNA-binding of the Rb-E2F complex involves another cellular factor. Addition of Rb to purified preparations of E2F does not generate an Rb-E2F complex that can bind DNA, and in fact, we see an inhibition of the DNA-binding ability of E2F. On the other hand, addition of Rb to cruder preparations of E2F results in the formation of an Rb-E2F complex (E2Fr) that can bind DNA and produces a distinct complex in gel retardation assays. We have identified and purified a 60-kDa protein that allows the Rb-E2F complex to bind DNA, and we show that this 60-kDa protein exerts its effect by directly interacting with Rb.
Animals↗
Interaction of central serotonin and dopamine in the regulation of carbaryl-induced tremor.
Carbaryl (50-200 mg/kg, p.o.) produced dose-dependent tremors and inhibition of striatal AChE activity. A dose-dependent elevation of striatal 5-HT and 5-HIAA levels was also observed with carbaryl but at the higher doses (100-200 mg/kg p.o.). L-Trp or 5-HTP or haloperidol potentiated the carbaryl-induced tremors. Further, 5-HTP or haloperidol, when administered (i) alone, reduced the ED50 value and increased the duration of carbaryl-induced tremors without affecting the maximum tremorogenic response of rats and (ii) together, did not change any of these measures significantly. Atropine (acetylcholine antagonist) completely blocked the tremors produced by carbaryl in the absence or presence of 5-HTP or haloperidol. Methysergide (5-HT antagonist) and bromocriptine (DA agonist) antagonised the potentiating effect of 5-HTP and haloperidol, respectively, on the carbaryl-induced tremors. Furthermore, bromocriptine antagonised the potentiating effect of 5-HTP on the carbaryl-induced tremor but, methysergide failed to achieve this antagonism in presence of haloperidol. These results indicate that carbaryl-induced tremors primarily involve the activation of central cholinoceptors and that the serotonergic potentiation of carbaryl-induced tremors is possibly mediated through the dopaminergic disinhibition of cholinergic neurons.
5-Hydroxytryptophan↗