Biomedical subjects
Publications and source records attributed to S Pandit.
Aortoarteritis presenting with isolated bilateral coronary artery ostial stenosis is a serious but rare condition. This letter emphasizes on a very atypical presentation of aortoarteritis and also distinct but unusual form of angiographic findings involving total occlusion of left main coronary artery from the ostium and tight ostial right coronary artery stenosis that had a fulminant disease course.
The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS-PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system.
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Minocycline-induced dark pigmentation has been described affecting the oral cavity (teeth, mucosa, alveolar bone), skin, nails, eyes and thyroid. To date, there is no report of other bones being affected. We report a case of black pigmentation of the acromian in a patient who had used minocycline on a long-term basis for acne rosecea. Biopsy of the iliac crest revealed that the pelvis was also affected.
The effect of Himoliv (HV) was evaluated in carbon tetrachloride or paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of either carbon tetrachloride (CCl4, 1 ml/kg, 50% v/v with olive oil, s.c.) or paracetamol (PC, 1 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (ALP) and hepatic thiobarbituric acid reacting substances (TBARS) and superoxide dismutase (SOD). HV pretreatment (0.5 and 1.0 ml/kg, p.o.) significantly (P < 0.001) reduced CCl4 or PC-induced elevations of the levels of SGOT, SGPT, ALP and TBARS, while the reduced concentration of SOD due to CCl4 or PC was reversed. Silymarin (25 mg/ kg, p.o.), a known hepatoprotective drug showed similar results.
To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.
The treatment of relapsed multiple myeloma remains a challenge for clinicians. Most salvage therapies result in transient responses, with median survival from relapse ranging from 6 to 18 months. No randomized trials comparing salvage therapies have been performed. In the absence of a "gold standard" salvage therapy, relapsed patients should be considered for clinical trials. In light of the recent observation that thalidomide alone brings about a 30% to 35% response rate with manageable toxicities, this is the most promising single agent available to treat relapsed disease. The maximum effective dose appears to be 400 mg/d; virtually all responses are evident within 2 months of starting therapy. Combination therapy of thalidomide with pulse dexamethasone or other chemotherapeutic agents has shown promise in pilot trials. Even with thalidomide-responsive disease, the response duration is brief, ranging from 3 to 6 months. Therefore, the authors recommend that patients under the age of 78 years who have acceptable physiologic organ function, chemotherapy-sensitive disease, third-party financial coverage, and adequate hematopoietic stem cells be considered for high-dose therapy with autologous hematopoietic stem cell transplant. High-dose therapy with hematopoietic stem cell transplant provides the highest response rate, response duration, and survival compared with historical controls treated with conventional therapy. Patients under the age of 70 years who have human leukocyte antigen-compatible donors should be considered for immune-based therapy using nonmyeloablative preparative regimens with allogeneic hematopoietic stem cell transplant.
In Escherichia coli, rRNA operons are transcribed as 30S precursor molecules that must be extensively processed to generate mature 16S, 23S and 5S rRNA. While it is known that RNase III cleaves the primary transcript to separate the individual rRNAs, there is little information about the secondary processing reactions needed to form their mature 3' and 5' termini. We have now found that inactivation of the endoribonuclease RNase E slows down in vivo maturation of 16S RNA from the 17S RNase III cleavage product. Moreover, in the absence of CafA protein, a homolog of RNase E, formation of 16S RNA also slows down, but in this case a 16.3S intermediate accumulates. When both RNase E and CafA are inactivated, 5' maturation of 16S rRNA is completely blocked. In contrast, 3' maturation is essentially unaffected. The 5' unprocessed precursor that accumulates in the double mutant can be assembled into 30S and 70S ribosomes. Precursors also can be processed in vitro by RNase E and CafA. These data indicate that both RNase E and CafA protein are required for a two step, sequential maturation of the 5' end of 16S rRNA, and that CafA protein is a new ribonuclease. We propose that it be renamed RNase G.
Ayurvedic preparations of metallic iron commonly categorised as different 'putas' of 'Louha Bhasma' was chemically analysed and pharmacologically investigated in iron deficiency anemia. Atomic absorption spectral (AAS) study of different putas of Louha Bhasma revealed the presence of various proportions of important metals along with varied concentration of iron in it. The effect of a representative puta viz. 50 puta of Louha Bhasma in the management of agar gel diet and phlebotomy induced iron deficiency anemia in animal model was found to be statistically highly significant (P < 0.001) in comparison to the control and standard drug Fefol treated groups.
Ribosomal RNAs are generally synthesized as long, primary transcripts that must be extensively processed to generate the mature, functional species. In Escherichia coli, it is known that the initial 30S precursor is cleaved during its synthesis by the endonuclease RNase III to generate precursors to the 16S, 23S, and 5S rRNAs. However, despite extensive study, the processes by which these intermediate products are converted to their mature forms are poorly understood. In this article, we describe the maturation of 23S rRNA. Based on Northern analysis of RNA isolated from a variety of mutant strains lacking one or multiple ribonucleases, we show that maturation of the 3' terminus requires the action of RNase T, an enzyme previously implicated in the end turnover of tRNA and in the maturation of small, stable RNAs. Although other exoribonucleases can participate in shortening the 3' end of the initial RNase III cleavage product, RNase T is required for removal of the last few residues. In the absence of RNase T, 23S rRNA products with extra 3' residues accumulate and are incorporated into ribosomes, with only small effects on cell growth. Purified RNase T accurately and efficiently converts these immature ribosomes to their mature forms in vitro, whereas free RNA is processed relatively poorly. In vivo, the processing defect at the 3' end has no effect on 5' maturation, indicating that the latter process proceeds independently. We also find that a portion of the 23S rRNA that accumulates in many RNase T- cells becomes polyadenylated because of the action of poly(A) polymerase I. The requirement for RNase T in 23S rRNA maturation is discussed in relation to a model in which only this enzyme, among the eight exoribonucleases present in E. coli, is able to efficiently remove nucleotides close to the double-stranded stem generated by the pairing of the 5' and 3' termini of most stable RNAs.
Polyadenylation at the 3' terminus has long been considered a specific feature of mRNA and a few other unstable RNA species. Here we show that stable RNAs in Escherichia coli can be polyadenylated as well. RNA molecules with poly(A) tails are the major products that accumulate for essentially all stable RNA precursors when RNA maturation is slowed because of the absence of processing exoribonucleases; poly(A) tails vary from one to seven residues in length. The polyadenylation process depends on the presence of poly(A) polymerase I. A stochastic competition between the exoribonucleases and poly(A) polymerase is proposed to explain the accumulation of polyadenylated RNAs. These data indicate that polyadenylation is not unique to mRNA, and its widespread occurrence suggests that it serves a more general function in RNA metabolism.
In addition to tRNA and 5S RNA, Escherichia coli contains several other small, stable RNA species; these are M1, 10Sa, 6S, and 4.5S RNA. Although these RNAs are initially synthesized as precursor molecules, relatively little is known about their maturation. The data presented here show that 3' exoribonucleolytic trimming is required for the final maturation of each of these molecules. As found previously with tRNA, but not 5S RNA, any one of a number of exoribonucleases can carry out the trimming reaction in vivo, although RNases T and PH are most effective. In their absence, large amounts of immature molecules accumulate for most of the RNAs, and these can be converted to the mature forms in vitro by the purified RNases. A model is proposed that identifies a structural feature present in all the small, stable RNAs of E. coli, and describes how this structure together with the RNases influences the common mechanism for 3' maturation.
BACKGROUND: We investigated whether a recently restructured pediatric intensive care unit (PICU) had a decrease in the cost of patient care over the years. METHODS: We retrospectively studied 89 previously healthy patients admitted to the PICU of a community-based, university-affiliated teaching hospital over a 4-year period (1991 to 1994) for treatment of lower airway disease. Data collected were patient age, severity of illness, length of stay in both PICU and hospital, prorated hospital bill, year of admission, and patient-specific PICU-originated costs (POC). RESULTS: There was a decrease of POC over the 4-year period, though two factors were associated with a cost increase in this group of patients: an increase in the severity of illness and intubation. The decrease over the years remained present even when excluding intubated patients and adjusting for severity of illness. A decline of 58% below the initial cost for diagnostic tests was the most prominent of all the individual areas studied. Decreases in POC correlated with decreases in the prorated hospital bill. CONCLUSIONS: The costs of management for these previously healthy patients treated for lower airway disease decreased over the study period. We speculate that the time related decrease in costs is a reflection of the learning curve of the pediatric critical care team. The decrease in POC did not shift costs to other areas of the hospital.
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To study the functions of DNA topoisomerase I and Hpr1 protein, a suppressor mutant of the temperature-sensitive growth of an hpr1 top1-5ts double mutant was isolated. The isolated triple mutant showed cold-sensitive growth. By complementation of this phenotype, the suppressor gene was cloned. DNA sequencing showed it to be GCR3, a gene involved in the expression of glycolytic genes. Further analysis showed that gcr3 mutations also suppressed the temperature-sensitive growth of hpr1 single mutants. Experiments with gcr3 truncation mutants also suggested a genetic interaction between GCR3 and HPR1. The fact that top1 suppressed the growth defect of gcr3 suggested an interaction between those two genes also. Plasmid DNA isolated from gcr3 mutants was significantly more negatively supercoiled than normal, suggesting that Gcr3 protein, like topoisomerase I and Hpr1p, affects chromatin structure, perhaps during transcription.
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Foam tape used to protect epidural catheters during immersion in a Dornier HM3 lithotriptor was identified retrospectively as the cause of poor stone fragmentation. Studies of shock wave penetration through various protective type materials indicate that a particular water repellant tape is least likely to impair shock wave penetration.
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