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Biomedical subjects

S Joshi

Publications and source records attributed to S Joshi.

At least 109 records · Page 6Linked to original sources

A prospective evaluation of clinical tests for placement of laryngeal mask airways.

BACKGROUND: Reliable tests of correct anatomic placement of the laryngeal mask airway (LMA) may enhance safety during use and minimize the need for fiberoptic instrumentation during airway manipulation through the device. This study assessed the correlation between the outcomes of nine clinical tests to place the LMA and the anatomic position of the device as graded on a standard fiberoptic scale. METHODS: During 150 anesthetics, the outcome of nine clinical tests of correct placement was individually scored as satisfactory (positive) or unsatisfactory (negative) for clinical use of the LMA. Anatomic placement was assessed (by fiberoptic evaluation) by an anesthesiologist, who was blinded to the placement of the device, as grade 1, vocal cords not seen; grade 2, cords plus the anterior epiglottis seen; grade 3, cords plus the posterior epiglottis seen; and grade 4, only vocal cords seen. The outcomes of clinical tests were correlated with fiberoptic grade. RESULTS: Tests that correlated with the fiberoptic grade were the ability to generate an airway pressure of 20 cm water, the ability to ventilate manually, a black line on the LMA in midline, anterior movement of the larynx, outward movement of the LMA on inflation of the cuff, and movements of the reservoir bag with spontaneous breathing. Two tests, ability to generate airway pressure of 20 cm water and ability to ventilate manually, correlated with fiberoptic grades 4 and 3 combined (i.e., the epiglottis was supported by the LMA) and grade 2 (the epiglottis was not supported by the LMA). Tests with poor correlation with fiberoptic grade were the presence of resistance at the end of insertion, inability to advance LMA after inflation of the cuff, and presence of a capnographic trace. CONCLUSIONS: The outcome of clinical tests correlates with the anatomic placement of LMAs, as judged by fiberoptic examination. Two tests that best correlated with the fiberoptic grade were the ability to generate airway pressure of 20 cm water and the ability to ventilate manually.

Adult↗

Infectious complications of propionic acidemia in Saudia Arabia.

A retrospective study of 38 patients with propionic acidemia indicates a high frequency of infections; affecting 80% of such patients. The Saudi Arabian population studied is a product of consanguineous marriages, and presents with a severe phenotype. Most microorganisms implicated are unusual, which suggests an underlying immune deficiency. These frequent infections occur despite aggressive treatment with appropriate diets, carnitine and during acute episodes of the disease with metronidazole, which suggests a global effect of the disease on T and B lymphocytes as well as on the bone marrow cells. Any patient with propionic acidemia should be closely followed up for an intercurrent infection in association with acute metabolic decompensation.

Acidosis↗

Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations.

PURPOSE: The purpose of this study was to define the influence of feeding mean arterial pressure (FMAP) in conjunction with other morphological or clinical risk factors in determining the probability of hemorrhagic presentation in patients with cerebral arteriovenous malformations (AVMs). METHODS: Clinical and angiographic data from 340 patients with cerebral AVMs from a prospective database were reviewed. Patients were identified in whom FMAP was measured during superselective angiography. Additional variables analyzed included AVM size, location, nidus border, presence of aneurysms, and arterial supply and venous drainage patterns. The presence of arterial aneurysms was also correlated with site of bleeding on imaging studies. RESULTS: By univariate analysis, exclusively deep venous drainage, periventricular venous drainage, posterior fossa location, and FMAP predicted hemorrhagic presentation. When we used stepwise multiple logistic regression analysis in the cohort that had FMAP measurements (n = 129), only exclusively deep venous drainage (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.4 to 9.8) and FMAP (OR, 1.4 per 10 mm Hg increase; 95% CI, 1.1 to 1.8) were independent predictors (P < 0.01) of hemorrhagic presentation; size, location, and the presence of aneurysms were not independent predictors. There was also no association (P = 0.23) between the presence of arterial aneurysms and subarachnoid hemorrhage. CONCLUSIONS: High arterial input pressure (FMAP) and venous outflow restriction (exclusively deep venous drainage) were the most powerful risk predictors for hemorrhagic AVM presentation. Our findings suggest that high intranidal pressure is more important than factors such as size, location, and the presence of arterial aneurysms in the pathophysiology of AVM hemorrhage.

Adult↗

Height velocity, body fat and menarcheal age of Indian girls.

OBJECTIVE: To understand the onset of menarche in relation to changes in physical measurements that take place during adolescence, especially the changes in height velocity and changes in body fat. DESIGN: Adolescent girls in the 9-16 year age group were observed longitudinally every six months for a period of two years. SETTING: Girls from schools catering to urban high socio-economic class (HSE, n = 135) and those catering to low socio-economic class (LSE, n = 398) were evaluated. METHODS: Six monthly measurements of weight, height and triceps skinfold thickness (TSFT) were done. Menarcheal age was recorded by recall method for the girls who were menstruating at the beginning of the study and prospectively for girls whose onset was after the initiation of the study. Body fat (%) was estimated using weight, height and TSFT. RESULTS: The girls from LSE not only had lower attained weight, height, skinfold thickness at triceps and body fat but also had a significant difference (p < 0.05) in menarcheal age (15.4 yr) as compared to girls from HSE (12.1 yr). Although social class differences delayed the occurrence of the event by chronological age, the time between peak height velocity (PHV) and onset of menarche remained similar (1.5 yr) irrespective of social class. The mean weight at menarche, at group level (but not at individual level), was around 38 kg in both socio-economic classes, irrespective of age at onset. Further menarche represented the point of maximum deceleration in height velocity and maximum acceleration in body fat in both social classes. CONCLUSION: Our data indicated a partial support for critical weight hypothesis and suggested that these limits vary from community to community. The analysis revealed that rather than absolute values of weight, height and body fat, changes in these measurements are of significance with regard to onset of menarche.

Adipose Tissue↗

Differential coupling of mu-, delta-, and kappa-opioid receptors to G alpha16-mediated stimulation of phospholipase C.

The mu-opioid receptor has recently been shown to stimulate phosphoinositide-specific phospholipase C via the pertussis toxin-sensitive G16 protein. Given the promiscuous nature of G16 and the high degree of resemblance of signaling properties of the three opioid receptors, both delta- and kappa-opioid receptors are likely to activate G16. Interactions of delta- and kappa-opioid receptors with G16 were examined by coexpressing the opioid receptors and G alpha16 in COS-7 cells. The delta-selective agonist [D-Pen2,D-Pen5] enkephalin potently stimulated the formation of inositol phosphates in cells coexpressing the delta-opioid receptor and G alpha16. The delta-opioid receptor-mediated stimulation of phospholipase C was absolutely dependent on the coexpression of G alpha16 and exhibited appropriate ligand selectivity and dose dependency. Similar transfection studies revealed only weak stimulation by the mu-opioid receptor, whereas the kappa-opioid receptor produced moderate phospholipase C activity. G alpha16 thus appeared to interact differentially with the three opioid receptors. Radioligand binding assays indicate that the mu-opioid receptor was expressed at a lower level than those of the delta- and kappa-opioid receptors. To examine if differential coupling to G alpha16 is prevalent, a panel of Gs- or Gi-coupled receptors was coexpressed with G alpha16 in COS-7 cells and assayed for agonist-induced stimulation of phospholipase C. Activation of alpha2- and beta2-adrenergic, dopamine D1 and D2, adenosine A1, somatostatin-1 and -2, C5a, formyl peptide, and luteinizing hormone receptors all resulted in stimulation of phospholipase C, with maximal stimulations ranging from 1.5- to almost 17-fold. These findings suggest that the promiscuous G alpha16 can in fact discriminate among different receptors and that such preferential interaction might in part be due to the abundance of receptors.

Analgesics, Opioid↗

Oligomycin sensitivity conferring protein (OSCP) of bovine heart mitochondrial ATP synthase: high-affinity OSCP-Fo interactions require a local alpha-helix at the C-terminal end of the subunit.

Earlier studies on oligomycin sensitivity conferring protein (OSCP) of bovine mitochondrial ATP synthase (F1Fo) indicated that a deletion mutant form (CD-10), lacking the last 10 amino acid residues (K181-L190), was unable to bind to the Fo segment, or reconstitute energy-linked reactions in OSCP-depleted F1Fo complexes [Joshi et al. (1996) Biochemistry 35, 12094-12103]. So far as known, the K181-L190 region of all mammalian species of OSCP harbors four charged residues at positions 181, 184, 187, and 188, while secondary structure predictions suggest that the K178-M186 region has a high propensity to form a helix [Ovchinnikov et al. (1984) FEBS Lett. 166, 19-22; Higuti et al. (1993) Biochim. Biophys. Acta 1172, 311-314; Grinkevich et al. ( 1994) Biol. Membr. 11, 310-323; Engelbrecht et al. (1991) Z. Naturforsch., C: Biochem., Biophys., Biol.,Virol. 46, 759-764]. Present studies were undertaken to clarify the role of individual amino acids in the K181-L190 region in OSCP-stimulated energy coupling. Our data show that simultaneous replacements of all four charged residues by uncharged but polar glutamines, or of K181-R184 by apolar alanines, had no significant influence either on the total alpha-helix content of the mutant forms or on the ability of mutant OSCPs to couple energy-linked reactions. However, a substitution of the K181-M186 region by six proline residues led to complete loss in the coupling activity of the resultant mutant. A detailed analysis of the 6-proline mutant form revealed that the variant was indistinguishable from WT OSCP with respect to expression characteristics, affinity for S-Sepharose, and ability to interact with F1, but was unable to complex with the Fo segment. These studies suggest that the global protein structure was not destabilized. The helix potential prediction analyses showed that the 6-proline OSCP displayed a marked decrease in the helix-forming propensity in the region corresponding to residues 175-190. Quantitative CD analyses to measure helical content demonstrated that both of the mutant forms 6-proline-OSCP and CD-10 had a somewhat lower alpha-helical content compared to WT protein, while synthetic peptides corresponding in sequence to the K178-L190 region displayed a high propensity to form a helix. Taken together, these results suggest that the C-terminal end of OSCP encompasses an alpha-helix which is crucial for high-affinity interactions of the C-terminal end of this subunit with Fo in the F1Fo enzyme.

Adenosine Triphosphatases↗

Co-packaging of non-vector RNAs generates replication-defective retroviral vector particles: a novel approach for blocking retrovirus replication.

A Moloney murine leukemia virus (MoMuLV)-derived packaging retroviral vector, pUCMoTN-PR3, was previously developed in which the packaging (psi) signal was cloned within the 5'-long terminal repeat (LTR) U3-r and U5 sequences. The MoTN-PR3 vector particles released from a transfected packaging cell line contain RNAs with r-psi-U5 sequences at the 5'-end and U3-r sequences at the 3'-end. Upon infection, these vector particles can efficiently transduce the neomycin phosphotransferase (neo) gene to the target cells. The structure of the proviral DNA synthesized in these cells was shown to contain modified 5'- and 3'-LTRs with U3-r-psi-U5 sequences, indicating that this vector can undergo reverse transcription and integration. Analysis of psi signal-containing RNAs revealed that in addition to vector RNA transcribed from the MoMuLV 5'-LTR promoter, readthrough neo RNA transcribed from the internal herpes simplex virus (HSV) thymidine kinase (tk) promoter and cellular RNAs transcribed from the MoMuLV 3'-LTR promoter are produced. Of these, the downstream cellular RNAs are also packaged within the vector particles. These vector particles containing the vector and non-vector RNAs carrying the MoMuLV psi signal are non-infectious. It is proposed that intracellular expression of packageable non-viral RNAs may represent an effective strategy for inhibiting animal and plant virus replication.

3T3 Cells↗

Inhibition of HIV-1 replication by retroviral vectors expressing monomeric and multimeric hammerhead ribozymes.

Retroviral vectors were engineered to express monomeric and multimeric hammerhead ribozymes targeting one and nine highly conserved sites within the HIV-1 envelope (Env) coding region. In vitro, both the monomeric and multimeric ribozymes were shown to be active and cleave the target RNA containing the cleavage sites. A human CD4+ T lymphocyte-derived MT4 cell line was stably transduced with retroviral vectors expressing these ribozymes. Ribozyme expression in stably transduced cells was confirmed by Northern blot analysis and reverse-transcription polymerase chain reaction (RT-PCR). As compared with the control cells lacking any ribozyme, HIV-1 replication was delayed in monomeric RzEnv-expressing cells. Virus replication was almost completely inhibited in multimeric RzEnv1-9-expressing cells as no viral RNA or protein could be detected in these cells and in their culture supernatants for up to 60 days after infection. The genomic DNA from RzEnv1-9-expressing cells was shown to contain HIV-1 proviral DNA sequences at days 3 and 60 after HIV infection. HIV-1 used in the challenge experiments was found to contain fully reverse transcribed '-' strand DNA which should have been able to infect complete proviral DNA synthesis and integrate within the cellular genome without being affected by pre-existing ribozymes. Therefore, the proviral DNA present at day 3 after infection may have originated from infection by such DNA-containing virus particles. The results obtained with the retroviral vector expressing RzEnv1-9 are very encouraging and we envisage its future use in anti-HIV-1 gene therapy.

CD4-Positive T-Lymphocytes↗

Acupressure treatment for prevention of postoperative nausea and vomiting.

Postoperative nausea and vomiting are still common problems after general anesthesia, especially in ambulatory surgery. Drug therapy is often complicated with central nervous system symptoms. We studied a nonpharmacological method of therapy--acupressure--at the Pericardium 6 (P.6) (Nei-Guan) meridian point. Two hundred consecutive healthy patients undergoing a variety of short surgical procedures were included in a randomized, double-blind study: 108 patients were in the acupressure group (Group 1) and 92 patients were in the control group (Group 2). Spherical beads of acupressure bands were placed at the P.6 points in the anterior surface of both forearms in Group 1 patients, while in Group 2 they were placed inappropriately on the posterior surface. The acupressure bands were placed before induction of anesthesia and were removed 6 h postoperatively. They were covered with a soft cotton wrapping to conceal them from the blinded observer who evaluated the patients for presence of nausea and vomiting and checked the order sheet for any antiemetics prescribed. In both groups, the age, gender, height, weight, and type and duration of surgical procedures were all comparable without significant statistical difference. In Group 1, only 25 of 108 patients (23%) had nausea and vomiting as compared to Group 2, in which 38 of 92 patients (41%) had nausea and vomiting (P = 0.0058). We concluded that acupressure at the P.6 (Nei-Guan) point is an effective prophylaxis for postsurgical nausea and vomiting and therefore a good alternative to conventional antiemetic treatment.

Acupressure↗

Manipulation of cerebrovascular resistance during internal carotid artery occlusion by intraarterial verapamil.

UNLABELLED: Occlusion of the internal carotid artery (ICA) results in acute cerebral hypotension. We hypothesized that during acute cerebral hypotension, in addition to physiological autoregulation, further arteriolar relaxation is possible by pharmacological means. We tested the feasibility of using intracarotid verapamil, a calcium channel blocker, to decrease the cerebrovascular resistance (CVR) and augment cerebral blood flow (CBF) at low postocclusion distal ICA pressures (PICA). Eleven patients undergoing trial occlusion of ICA were enrolled. Distal ICA or stump pressure, hemispheric CBF, and CVR were determined before and after carotid occlusion. During ICA occlusion, CBF and other physiological variables were determined before and after intracarotid verapamil. Two patients were excluded from the study. Carotid occlusion (n = 9) significantly decreased PICA (mean +/- SD, from 82 +/- 22 to 46 +/- 11 mm Hg, P = 0.001) and CBF (from 42 +/- 11 to 33 +/- 11 mL.100 g-1.min-1, P < 0.05). During occlusion, after intracarotid verapamil (3.9 +/- 1.6 mg), hemispheric CBF tended to increase from 31 +/- 11 to 35 +/- 14 mL.100 g-1.min-1 (P = 0.067). However, the percent increase in CBF after verapamil was a linear function of PICA (y = 1.01 x -32, n = 9, r2 = 0.84, P = 0.006). The decrease in CBF during carotid occlusion suggests that near maximal cerebral autoregulatory vasodilation had occurred, although our results indicate that it may be feasible to further augment CBF by pharmacological means during acute cerebral hypotension. IMPLICATIONS: When the internal carotid artery is occluded during neurosurgical procedures, there may be a significant reduction in cerebral perfusion. The authors have demonstrated that the intraarterial administration of verapamil increases cerebral blood flow as a linear function of cerebral artery pressure. Intracarotid injection of vasodilators may augment cerebral blood flow during acute cerebral hypotension.

Adult↗

Cerebral arteriovenous malformation feeding artery aneurysms: a theoretical model of intravascular pressure changes after treatment.

OBJECTIVE: A quantitative model may be used to estimate the magnitude of expected pressure changes along the vascular tree with shunt ablation and may provide information to assess the hemodynamic risk of arteriovenous malformation (AVM) treatment. METHODS: A computer model of the cerebral circulation was applied to estimate the changes in intravascular pressure, velocity, biomechanical stress, and shear stress that might be expected from either endovascular or surgical ablation of AVMs. Two AVM sizes and two feeding artery constellations were simulated. The effect of different shunt flows on vascular pressure was modeled. In each simulation, AVMs were occluded in a stepwise fashion. The effects of systemic hypertension and hypotension in various vascular zones were also simulated. RESULTS: As large (1000 ml/min) AVMs were occluded, the mean feeding arterial pressure increased from 18 to 68 mm Hg; the percent-occlusion at half-maximal pressure increase was 92%. For medium (500 ml/min) AVMs, feeding arterial pressure increased from 37 to 66 mm Hg; the percent-occlusion at half-maximal pressure increase was 71%. During manipulation of systemic pressure, hemodynamic changes in the circulation close to the nidus were proportionally less than changes in systemic pressure; the degree of proportionality depended on the magnitude of AVM shunt flow. CONCLUSION: In this simulation, shunt obliteration increased pressure in the nidus and feeding arteries with little effect on the proximal circulation. The shunt provided a "buffering" effect, i.e., higher flow fistulas were exposed to smaller variations in intravascular pressure in feeding artery and nidal pressures during manipulation of systemic pressure.

Adult↗

Noise reduction for NMR FID signals via Gabor expansion.

The parameters in a nuclear magnetic resonance (NMR) free induction decay (FID) signal contain information that is useful in biological and biomedical applications and research. A real time-sampled FID signal is well modeled as a finite mixture of modulated exponential sequences plus noise. We propose to use the generalized Gabor expansion for noise reduction, where the generalized Gabor expansion represents a signal in terms of a collection of time-shifted and frequency-modulated versions of a single sequence (prototype sequence). For FID signal-fitting, we choose the exponential sequence as the prototype function. Using the generalized Gabor expansion and exponential prototype sequences for FID model-fitting, an NMR FID signal can be well represented by the Gabor coefficients distributed in the joint time-frequency domain (JTFD). The Gabor coefficients reflect the weights of modulated exponential sequences in a signal. One of the important features is that the nonzero Gabor coefficients of a modulated exponential sequence will span a very small area in the JTFD, whereas the Gabor coefficients of the noise will not. If the exponent constant of the prototype sequence in the generalized Gabor expansion matches that of a modulated exponential sequence in the signal, then only one of the Gabor coefficients is nonzero in the JTFD. This is a very important property since it can be exploited to separate a signal from noise and to estimate modulated exponential sequence parameters.

Linear Models↗

Role of amino- and carboxyl-terminal regions of G(alphaZ) in the recognition of Gi-coupled receptors.

Many Gi-coupled receptors are known to interact with the pertussis toxin (PTX)-insensitive Gz protein. Given that the alpha subunits of Gi and Gz share only 60% identity in their amino acid sequences, their receptor-interacting domains must be highly similar. By swapping the carboxyl termini of alpha i2 and alpha z with each other or with those of alpha t, alpha12, and alpha13, we examined the relative contributions of the carboxyl-end 36 amino acids of the alpha chains toward receptor recognition. Chimeric alpha chains lacking the site for PTX-catalyzed ADP-ribosylation were coexpressed with the type II adenylyl cyclase (AC II) and one of several Gi-coupled receptors (formyl peptide, dopamine D2, and delta-opioid receptors) in human embryonic kidney 293 cells. The alpha i2/alpha z chimera was able to interact with both aminergic and peptidergic receptors, resulting in betagamma-mediated stimulation of AC II in the presence of agonists and PTX. Functional and mutational analyses of alpha i2/alpha z revealed that this chimera can inhibit the endogenous ACs of 293 cells. Similarly, the alpha z/alpha i2 chimera seemed to retain the abilities to interact with receptors and inhibit cAMP accumulation. Fusion of the carboxyl-terminal 36 amino acids of alpha z to a backbone of alpha t1 produced a chimera, alpha t1/alpha z, that did not couple to any of the Gi-coupled receptors tested. Interestingly, an alpha13/alpha z chimera (with only the last five amino acids switched) displayed differential abilities to interact with receptors. Signals from aminergic, but not peptidergic, receptors were transduced by alpha13/alpha z. A similar construct, alpha12/alpha z, behaved just like alpha13/alpha z. These results indicated that "alpha i-like" or "alpha z-like" sequences at the carboxyl termini of alpha subunits are not always necessary or sufficient for specifying interaction with Gi-coupled receptors.

Adenylate Cyclase Toxin↗

A rapid and efficient system for screening HIV-1 Pol mRNA-specific ribozymes.

Hammerhead ribozymes are potentially important tools for suppressing intracellular expression of unwanted RNAs. However, the reports that exist on their activity against different targets have described mixed success. As an initial step towards developing a rapid and effective system for in vivo testing of ribozymes, two human immunodeficiency virus type-1 (HIV-1) polymerase (Pol) mRNA-specific ribozymes, RzPro directed against the protease (Pro) coding region and RzRT directed against the reverse transcriptase (RT) coding region, were designed and tested in Escherichia coli. Both ribozymes displayed similar efficiencies in cleaving their target RNAs in vitro. RNA polymerase chain reaction was adapted to demonstrate the in vivo cleavage of RzPro and RzRT target sites. The resultant drop in HIV-1 RT activity was measured as well. The degree of suppression of RT activity was more apparent in vivo in cells expressing RzRT. The RT activity in cells expressing RzRT was shown to decrease by up to 96%. This system will be useful for rapid screening of (i) other ribozyme target sites within the Pol mRNA so that multitargeted ribozymes could be designed for use in anti-HIV-1 gene therapy, (ii) ribozymes with improved stability and catalytic activity, and (iii) cofactors, if any that could enhance ribozyme activity in vivo.

Base Sequence↗

Three-dimensional hippocampal MR morphometry with high-dimensional transformation of a neuroanatomic atlas.

PURPOSE: To test automated three-dimensional magnetic resonance (MR) imaging morphometry of the human hippocampus, to determine the potential gain in precision compared with conventional manual morphometry. MATERIAL AND METHODS: A canonical three-dimensional MR image atlas was used as a deformable template and automatically matched to three-dimensional MR images of 10 individuals (five healthy and five schizophrenic subjects). A subvolume containing the hippocampus was defined by using 16 landmarks that constrained the automated search for hippocampal boundaries. Transformation of the hippocampus template was automatically performed by using global pattern matching through a sequence of low-then high-dimensional translations, rotations, and scalings. RESULTS: The average test-retest volume difference measured with the automatic method was 3.1%, compared with the manual test-retest difference of 7.1%. Correlation between automated and manually determined volumes demonstrated the validity of the automated technique (intraclass correlation coefficient = .86). CONCLUSION: The automated method estimates hippocampal volumes with less variability (ie, lower variance) than that of manual out-lining.

Adult↗