Biomedical subjects
R Jain
Publications and source records attributed to R Jain.
Suprasellar tuberculoma presenting with diabetes insipidus and hypothyroidism--a case report.
Suprasellar tuberculomas are exceptionally rare and are even rarer in children. A case of suprasellar tuberculoma in a five year old male child who presented with diabetes insipidus, hypothyroidism and visual field defect is described. Deranged CSF parameters, imaging findings of a suprasellar rounded, peripherally enhancing lesion with thickening of the pituitary stalk, led to an accurate diagnosis of tuberculosis. The patient responded well to antituberculous treatment and an unnecessary surgery was avoided.
Structural basis of the anionic interface preference and kcat* activation of pancreatic phospholipase A2.
Pancreatic phospholipase A(2) (PLA2) shows a strong preference for the binding to the anionic interface and a consequent allosteric activation. In this paper, we show that virtually all the preference is mediated through 3 (Lys-53, -56, and -120) of the 12 cationic residues of bovine pancreatic PLA2. The lysine-to-methionine substitution enhances the binding of the enzyme to the zwitterionic interface, and for the K53,56,120M triple mutant at the zwitterionic interface is comparable to that for the wild type (WT) at the anionic interface. In the isomorphous crystal structure, the backbone folding of K53,56M K120,121A and WT are virtually identical, yet a significant change in the side chains of certain residues, away from the site of substitution, mostly at the putative contact site with the interface (i-face), is discernible. Such reciprocity, also supported by the spectroscopic results for the free and bound forms of the enzyme, is expected because a distal structural change that perturbs the interfacial binding could also affect the i-face. The results show that lysine-to-methionine substitution induces a structural change that promotes the binding of PLA2 to the interface as well as the substrate binding to the enzyme at the interface. The kinetic results are consistent with a model in which the interfacial Michaelis complex exists in two forms, and the complex that undergoes the chemical step is formed by the charge compensation of Lys-53 and -56. Analysis of the incremental changes in the kinetic parameters shows that the charge compensation of Lys-53 and -56 contributes to the activation and that of Lys-120 contributes only to the structural change that promotes the stability of the Michaelis complex at the interface. The charge compensation effects on these three residues also account for the differences in the anionic interface preference of the evolutionarily divergent secreted PLA2.
Enzymatic kinetic resolution of piperidine atropisomers: synthesis of a key intermediate of the farnesyl protein transferase inhibitor, SCH66336.
The resolution of secondary amines via enzyme-catalyzed acylation is a relatively rare process. The kinetic resolution of a series of intermediates of SCH66336 (1), by either enzymatic acylation of the pendant piperidine (4, 5) or hydrolysis of the corresponding carbamate 3, was investigated. In the case of 4, the molecule exists as a pair of enantiomers due to atropisomerism about the exocyclic double bond. The enzymatic acylation of (+/-)-4 was optimized in terms of acylating agent, solvent, and moisture content. The use of lipase, Toyobo LIP-300, and trifluoroethyl isobutyrate as acylating agent resulted in isobutyrylation of the (+)-enantiomer, which is easily separated from the unwanted (-)-4. Hydrolysis of the isobutyramide 6c yielded the desired (+)-4 in high enantiomeric excess. (-)-4 may be recovered from the resolution step, racemized, and resubjected to enzymatic acylation to increase material throughput.
Post-encephalitic Kluver-Bucy syndrome.
Kluver-Bucy syndrome is a rare amalgamation of neurobehavioural signs and symptoms seen infrequently in humans following insult to bilateral temporal lobes. This report presents a case which along with emerging symptoms of Kluver-Bucy syndrome, developed Attention-Deficit/Hyperactivity Disorder (ADHD) consequent to viral encephalitis. The case highlights the presentation and management of this syndrome in a six-year-old girl with primary focus on the implications of Kluver-Bucy symptoms in current clinical practice involving neurobehavioural syndromes in children.
Trafficking of non-regulated secretory proteins in insulin secreting (INS-1) cells.
AIMS/HYPOTHESIS: Sorting of proinsulin to the regulated secretory pathway of pancreatic beta cells and retention of insulin in dense-core granules of this pathway is remarkably efficient. To monitor the specificity of these events, the secretion of two exogenous secretory proteins not known to carry information for sorting or retention in the regulated pathway was investigated in INS-1 cells. METHODS: SEGFP, a fusion protein consisting of a signal peptide N-terminal to EGFP (mutant green fluorescent protein with enhanced fluorescence) and secreted alkaline phosphatase (SEAP) were expressed in INS-1 cells by transfection and by infection with recombinant adenovirus, respectively. Secretion of SEGFP was monitored by quantitative western blotting and that of SEAP by its activity. RESULTS: Secreted alkaline phosphatase showed high basal secretion (6.6% total) but only modest (3.6-fold) stimulation of secretion by secretagogues, in keeping with secretion largely through the constitutive pathway. By contrast SEGFP had a secretory pattern similar to insulin, with low basal secretion (0.8% total) and 16-fold stimulation by secretagogues. Granular localization of SEGFP was confirmed by high resolution electron microscopy immunocytochemistry. Pulse-chase experiments indicated retention of SEGFP in granules at least 24 h after synthesis. The secretory SEGFP, but not cytosolic EGFP, formed disulphide-linked oligomers. This could be implicated in its regulated secretion. CONCLUSION/INTERPRETATION: These data indicate that in INS-1 cells SEGFP, but not SEAP, is unexpectedly handled as a regulated secretory protein and stored along with insulin in granules. This raises questions about the specificity and mechanism of the sorting of proteins to granules in INS-1 cells or their retention therein or both.
Arnebins and antimicrobial activities of Arnebia hispidissima DC. cell cultures.
The whole plant of Arnebia hispidissima DC. (Boraginaceae) is used for the treatment of tongue and throat ailments in Indian traditional medicine. The present paper deals with the plants phytochemical constituents, the arnebins, and antimicrobial activities of its root extract. The antimicrobial activities were tested against Gram-positive and Gram-negative bacteria and fungi. The crude hexane extract demonstrated a potent antimicrobial effect against bacteria and a mild effect against fungi. Likewise, the hexane extract of cell cultures of A. hispidissima also showed mild bioefficacy against the select microorganisms.
Silicone intraocular lens compression and double lens implants in diseased eyes.
PURPOSE: To assess the outcomes of double lens implants in hyperoptic eyes with associated pathology. METHOD: Double lens implants were used in 4 eyes of 4 patients each with a different ophthalmic or neuro-ophthalmic disease. Biometry was performed in the standard contact fashion and lens power formulae used included SRK/T, Holladay and Hoffer Q. RESULTS: Average spherical equivalent refraction improved from +6.875 D to +0.38 D. Absolute average prediction error was greatest for SRK/T (2.65 D) and least for Holladay (1.73 D). Refractive suprises were influenced by the underlying disease process. One patient showed central lens compression. CONCLUSION: Underlying disease can produce biometry errors. Structural ophthalmic or neurological disease is not a contraindication to the use of double lens implants. Double lens implants are useful to correct refractive error in the presence of underlying disease.
Brain stem tuberculosis in children.
Tubercular meningitis and intracranial tuberculomas are the two frequent manifestations of neurotuberculosis with their variable incidence in different countries. Brain stem tuberculomas are even more unusual, accounting for 2.5-8% of all intracranial tuberculomas. We present here six paediatric cases of brain stem tuberculosis, where well-formed tuberculomas were demonstrated in five symptomatic cases; however, only a hypodense ill-defined lesion was found in the brain stem of one child who presented with features of tubercular meningitis. Three of these children had other associated tuberculomas in their brain parenchyma as well. All the six cases, however, showed the involvement of 3rd, 6th & 7th cranial nerves, in various combinations, at the time of initial presentation. Only two children developed hydrocephalus and required CSF diversion. All responded well to anti-tubercular chemotherapy, though two children developed toxicity to the therapy, which recovered with drug manipulation for about 2 months. Recovery was full without residual deficit in all the cases. Surgical excision of brain stem granulomas was not indicated in any case.
A large family of eukaryotic-like protein Ser/Thr kinases of Myxococcus xanthus, a developmental bacterium.
Myxococcus xanthus is a gram-negative bacterium that forms multicellular fruiting bodies upon starvation. Here, we demonstrate that it contains at least 13 eukaryotic-like protein Ser/Thr kinases (Pkn1 to Pkn13) individually having unique features. All contain the kinase domain of approximately 280 residues near the N-terminal end, which share highly conserved features in eukaryotic Ser/Thr kinases. The kinase domain is followed by a putative regulatory domain consisting of 185 to 692 residues. These regulatory domains share no significant sequence similarities. The C-terminal regions of 11 kinases contain at least 1 transmembrane domain, suggesting that they function as transmembrane sensor kinases. From the recent genomic analysis, protein Ser/Thr kinases were found in various pathogenic bacteria and coexist with protein His kinases. Phylogenetic analysis of these Ser/Thr kinases reveals that all bacterial Ser/Thr kinases were evolved from a common ancestral kinase together with eukaryotic Tyr and Ser/Thr kinases. Coexistence of both Ser/Thr and His kinases in some organisms may be significant in terms of functional differences between the two kinases. We argue that both kinases are essential for some bacteria to adapt optimally to severe environmental changes.
Urrets-Zavalia syndrome following trabeculectomy.
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Scleritis as a presenting feature of Takayasu's disease.
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Health status following recessional ulnar osteotomy.
This study describes the health status of 31 patients who underwent recessional ulnar osteotomy for ulnocarpal impingement. An additional lunotriquetral fusion was performed in 11/31 patients for joint degeneration. Outcomes included the DASH (Disability of arm, shoulder and hand) questionnaire, SF-36 Acute Health Survey, complications, and satisfaction with surgical outcome. Patients were stratified into two groups for analysis: osteotomy alone and osteotomy + fusion. The overall results indicated that osteotomy plus fusion in patients with more advanced ulnocarpal impingement did not equalise patients' post-operative health status to that reported by patients requiring osteotomy alone. Mean DASH and SF-36 physical component scores indicated better health status in the osteotomy group compared with the osteotomy + fusion group after surgery. Forty-one point nine per cent of patients required plate removal, and scar pain persisted in 58%. One patient in each group developed a non-union requiring revision surgery. Patients in both groups were generally satisfied with their surgical result, with a higher proportion of very or completely satisfied patients in the osteotomy group (65%) compared to the osteotomy + fusion group (27%). Overall, recessional ulnar osteotomy appears to be a successful procedure for the treatment of ulnocarpal impingement.
Endobronchial closure of a bronchopleural cutaneous fistula using angiography catheters.
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Retrocerebellar arachnoid cyst with syringomyelia: a case report.
Association of syringomyelia with retrocerebellar arachnoid cysts is rare. A case of 14 year old female is being reported, who presented with hydrocephalus caused by a large midline retrocerebellar infravermal arachnoid cyst leading to obstruction of the outlet foramina of the fourth ventricle. There was associated syringomyelia. The pathogenesis of syringomyelia is discussed. The need to evaluate cervical spinal cord by taking T1 weighted sagittal sections in all the patients of large posterior fossa mass lesions causing obstruction to the outlet foramina of the fourth ventricle has been stressed, in order to detect associated syringomyelia.
Cementless acetabular revision arthroplasty.
OBJECTIVE: To evaluate the effects of clinical factors on outcome after acetabular revision with a cementless beaded cup. DESIGN: Retrospective case series. SETTING: Tertiary care referral centre. PATIENTS: Forty-one patients who underwent acetabular revision with a cementless cup were followed up for a mean of 3.4 years. INTERVENTIONS: Acetabular revision with a beaded cementless cup in all patients. A morcellized allograft was used in 10 patients. OUTCOME MEASURES: A modified Harris hip score (range of motion measurement omitted), the SF-36 health survey, and the Western Ontario McMaster (WOMAC) osteoarthritis index. Multivariate analysis was used to evaluate the effects of age, gender, morcellized allografting, time to revision from the previous operation, acetabular screw fixation and concurrent femoral revision on outcome. RESULTS: Gender accounted for a significant portion of the variation seen in the SF-36 physical component scores (r = 0.36, p = 0.02), with women tending to have worse results. Increasing age was associated with lower WOMAC index function scores (r = 0.36, p = 0.03), whereas concurrent femoral revision tended to have a positive effect on WOMAC index function (r = 0.39, p = 0.01). None of the potential clinical predictors had any significant effect on the SF-36 mental component scores, or WOMAC index pain and stiffness scores. CONCLUSIONS: In cementless acetabular revision arthroplasty, physical function, as measured by generic and limb-specific scales, may be affected by gender, age and the presence of a concurrent femoral revision. Time to revision from the previous operation, morcellized allografting and screw fixation of the acetabulum did not affect outcomes. This information may provide some prognostic value for patients' expectations.
Functional outcome after acetabular revision with roof reinforcement rings.
OBJECTIVE: To evaluate the role for potential predictors of functional outcome after acetabular arthroplasty and to assess the results of revision with the use of a roof reinforcement ring. DESIGN: A retrospective case series. SETTING: A tertiary-care referral centre. PATIENTS: Twenty-four patients (average age 72.7 years) who had undergone acetabular revision with a roof reinforcement ring were followed up for an average of 2.8 years. INTERVENTIONS: Revision acetabular arthroplasty was performed using either the Mueller or Burch Schneider roof reinforcement ring, bone grafting and a cemented polyethylene cup. OUTCOME MEASURES: A modified Harris hip score (range of motion omitted), the SF-36 health survey and the Western Ontario McMaster (WOMAC) osteoarthritis index measured outcome. Multivariate analysis was used to determine the effects of certain clinical factors (age, sex, time to revision from previous hip operation and number of previous revisions) on outcome. RESULTS: Patients reported disability both on hip-specific and general health measures. The time to revision from previous operation positively correlated with SF-36 mental component scores (p = 0.003), WOMAC function (p = 0.04) and WOMAC pain (p = 0.03). Age, gender and number of past revisions did not affect outcome. CONCLUSIONS: Patients who undergo acetabular revision with a roof ring will continue to have some disability in the first 3 years after the procedure. A greater time between the previous operation and the revision operation is associated with a better outcome. Patients' expectations of postoperative results should be realistic in the face of a challenging reconstructive procedure.
Percussion of Traube's space--a useful index of splenic enlargement.
OBJECTIVE: To evaluate the sensitivity and specificity of palpation and percussion for splenic enlargement, as the accuracy of many of the clinical maneuvers we perform remains largely unstudied. METHODS: One hundred cases were selected at random from medical wards, and splenic enlargement was assessed by palpation and percussion of the Traube's space (Barkuns method), which was confirmed by the ultrasonography of the abdomen. The results of the various tests were tabulated and assessed statistically. RESULTS: 1) Performance of Traube's space percussion shows 24 true positive and 48 true negative cases, the test thus had an overall sensitivity of 67% and specificity of 75%. It was also found that the BMI of the false negative cases was significantly higher (29.43 Kg/m2). 2) Palpation as a diagnostic maneuver had a high specificity of 96.87% along with high false negative rate with overall low sensitivity of 44.44%. 3) Interpolation of findings of Traube's space percussion and palpation showed that maximum clinical utility could be achieved when both percussion and palpation were positive. CONCLUSION: Percussion of the Traube's space is a useful clinical screening test for splenomegaly, with a sensitivity of 67% and specificity of 75%, as compared to palpation (sensitivity of 44.44% and specificity of 96.87%). And maximum clinical utility is achieved when both percussion and palpation are combined.