Biomedical subjects
S Kumar
Publications and source records attributed to S Kumar.
Recovery of global nonrigid motion: a model-based approach without point correspondences
We present a novel technique for the estimation of global nonrigid motion of an object's boundary without using point correspondences. A complete description of the motion of an object's boundary involves specifying a displacement vector at each point of the boundary. Such a description provides a large amount of information, which needs to be processed further for study of the global characteristics of the deformation. Nonrigid motion can be studied hierarchically in terms of global nonrigid motion and point-by-point local nonrigid motion. The technique presented gives a method for estimating a global affine or polynomial transformation between two object boundaries. The novelty of the technique lies in the fact that it does not use any point correspondences. Our method uses hyperquadric models to model the data and estimate the global deformation. We show that affine or polynomial transformation between two datasets can be recovered from the hyperquadric parameters. The usefulness of the technique is twofold. First, it paves the way for viewing nonrigid motion hierarchically in terms of global and local motion. Second, it can be used as a front end to other motion analysis techniques that assume small motion. For instance, most nonrigid motion analysis algorithms make some assumptions on the type of nonrigid motion (conformal motion, small motion, etc.) that are not always satisfied in practice. When the motion between two datasets is large, our algorithm can be used to estimate the affine transformation (which includes scale and shear) or a polynomial transformation between the two datasets, which can then be used to warp the first dataset closer to the second so as to satisfy the small-motion assumption. We present experimental results with real and synthetic two- and three-dimensional data.
Insulin action enhancers for the management of type 2 diabetes mellitus.
Type 2 diabetes mellitus is a common metabolic disorder that has become a major public health problem because of the long-term microvascular and macrovascular complications associated with it. Tight glycaemic control has been shown to prevent complications, but a number of studies have shown that many patients with Type 2 diabetes have sub-optimal control. Insulin resistance is a fundamental abnormality in Type 2 diabetes but there have not been drugs that are able to reverse this defect. Thiazolidinediones (TZD) may, therefore, represent a breakthrough in the management of Type 2 diabetes as it is the first class of oral agents for diabetes that act as an insulin action enhancer to reduce insulin resistance. This review will examine available data on the currently available TZDs and consider its place in the management of Type 2 diabetes.
Repellency and toxicity of oil from Artemisia annua to certain stored-product beetles.
The essential oil of Artemisia annua L. was tested for its toxic repellent and development inhibitory activities against 2 economically important stored product insects: Tribolium castaneum (Herbst) and Callosobruchus maculatus (L.). Adult beetles of T. castaneum were repelled significantly by oil of A. annua at 1% concentration (vol:vol) and above in filter paper arena test. Dose-response relationship of A. annua oil revealed a significant negative correlation between larval survival; pupal survival and adult emergence of T. castaneum (i.e., increase in dose caused decrease in survival and adult emergence). Effective concentration (EC50) to reduce F1 progeny by 50% was calculated to be 2.6 and 4.1 microl/ml solvent against both the insect species, C. maculatus and T. castaneum, respectively. The relationship between bioactivity of oil from A. annua and responses of T. castaneum and C. maculatus is discussed. We found that oil from A. annua was largely responsible for both repellent (behavioral) and toxic (physiological) actions on 2 species of insect tested.
Ceiling culture of mature human adipocytes: use in studies of adipocyte functions.
Adipocytes contain large lipid droplets in their cytoplasm. When cultured, they float on top of the medium, clump together, and do not gain equal and sufficient access to the medium. Morphological changes cannot be observed and the majority of adipocytes undergo cell lysis within 72 h of isolation. We have used a ceiling culture method for human mature adipocytes which uses their buoyant property to allow them to adhere to a floating glass surface, where they remain viable for several weeks. Using confocal immunofluorescence microscopy we showed the cellular expression and subcellular localization of leptin in ceiling-cultured adipocytes. The secretion of leptin was increased from ceiling cultures following tumour necrosis factor-alpha treatment. Proliferation of mature human adipocytes in serum-containing medium was demonstrated by incorporation of bromodeoxyuridine, 2% of adipocytes showing positive incorporation after 4 h labelling. Proliferation was also evident from the budding of daughter cells. Apoptosis in the ceiling cultures was increased by 48 h serum deprivation (30-35 vs 10-15% in the control) and was assayed by propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling. Lipolysis, analysed by liquid scintillation counting, was increased by forskolin (10 microM for 90 min) and lipogenesis, shown by autoradiography, was stimulated by insulin (10 and 100 nM for 4 h). These findings indicate that ceiling-cultured adipocytes maintain adipocyte-specific functions and that ceiling culture, which overcomes the shortcomings of adipocyte suspension culture, can be used to study adipocyte cell biology.
Determination of transgene repeat formation and promoter methylation in transgenic plants.
The integration of transgenes into a plant host genome following Agrobacterium tumefaciens-mediated or direct transformation may occur as a single copy or in the form of tandem repeats. The latter has been associated with promoter methylation and silencing of transgenes. Thus, the early screening of such transgenic plants is desirable for ruling out future repeat-dependent transgene instability. We developed a simple PCR-based method in which primer pairs were specifically designed so that amplifications could only be obtained if the transgene was present in the form of multiple inserts in a transgenic line. The method was established using 35S-rolC transgenic aspen lines showing morphologically visible transgenic silencing. Later, it was possible to screen independent transgenic lines showing no visible marker gene expression. Furthermore, a method was developed in which positive PCR amplification was indicative of promoter methylation. The results were consistent and reproducible across different independent transgenic lines. The methods were quick, reliable, consistent and reproducible, and can be useful for routine screening of transgene silencing in lines derived from many different systems.
Client empowerment in psychiatry and the professional abuse of clients: where do we stand?
OBJECTIVE: There is a considerable imbalance of power in psychiatry that sits in favor of professionals. The abuse and discrimination of the mentally ill are not just restricted to the mental health system but may also exist in the primary care sector. This article aims to evaluate the effects of power imbalance on discrimination and abuse of people with mental illness by professionals. METHODS: A literature search was carried out on MEDLINE using the key words consumerism, client empowerment, abuse, and mental illness. Publications of two leading British consumer organizations: MIND and the Sainsbury Centre for Mental Health were hand searched. Relevant cross-references from the papers reviewed were consulted. Studies with information on the reasons for power imbalance and prevalence of discrimination and abuse of clients were critically reviewed. Explanations are offered as to why abuse and discrimination of clients by professionals may still occur despite the onset of the client empowerment movement. RESULTS AND DISCUSSION: The available evidence suggests that reasons for abuse of mental health clients fall under two broad categories: 1) direction from the imbalance of power and 2) those pertinent to the nature of physical or sexual abuse. Different grades of client empowerment and ways of strengthening it are described. CONCLUSIONS: There appears to be a link between power imbalance and abuse of clients with mental illness by professionals in all health care sectors. Client empowerment may help rectify the power imbalance. Prospective studies are required to establish whether client empowerment can reduce discrimination and abuse of clients and whether abuse is a consequence of power imbalance. Recommendations for future studies are made.
Inhibition of aminopeptidase P potentiates wheal response to bradykinin in angiotensin-converting enzyme inhibitor-treated humans.
Bradykinin is a nonapeptide that contributes to the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors. During ACE inhibition, an increased proportion of bradykinin is degraded through non-ACE pathways. Studies in animals suggest that aminopeptidase P (EC 3.4.11.9) may contribute to the metabolism of bradykinin. The purpose of the present study was to determine the contribution of aminopeptidase P to the degradation of bradykinin in humans in the presence and absence of ACE inhibition. To do this, we measured the wheal response to intradermal injection of bradykinin (0, 1, or 10 nicrog) in the presence or absence of intradermal administration of the specific aminopeptidase P inhibitor apstatin (5 or 10 microg) and oral administration of the ACE inhibitor quinapril (10 mg) in six healthy subjects. Both bradykinin (ANOVA; F = 101.18, P <.001) and apstatin alone (F = 7.01, P =.049) caused a wheal of dose-dependent size. There was no significant interaction between apstatin and bradykinin (F = 4.94, P =.175). Pretreatment with 10 mg of quinapril significantly shifted the dose-response curve for bradykinin to the left (effect of quinapril; F = 77.96, P <.001) and there was significant interaction between quinapril and bradykinin (F = 7.82, P =.041). The effect of quinapril was significantly potentiated by coinjection of 10 microg of apstatin (effect of apstatin; F = 21.60, P =.006), such that there was significant interactive effect of quinapril and apstatin (F = 20.83, P =.006) on the wheal response to bradykinin. Collectively, these data suggest that aminopeptidase P plays a minor role in the degradation of bradykinin in human skin in the absence of ACE inhibition but contributes significantly to the degradation of bradykinin in the presence of ACE inhibition.
Diphenhydramine disposition in the sheep maternal-placental-fetal unit: gestational age, plasma drug protein binding, and umbilical blood flow effects on clearance.
The objective of this study was to examine the interrelationships between maternal and fetal plasma drug protein binding, umbilical blood flow (Q(um)), gestational age (GA), and maternal-fetal diphenhydramine (DPHM) clearances in chronically instrumented pregnant sheep. Maternal and fetal DPHM placental (CL(mf) and CL(fm), respectively) and nonplacental (CL(mo) and CL(fo), respectively) clearances and steady-state plasma protein binding were determined in 18 pregnant sheep at 124 to 140 days' gestation (term, approximately 145 days). The data demonstrated a highly significant fall of approximately 66% in CL(fm) and a decreasing trend in CL(fo) ( approximately 47%) over the GA range studied. However, no such relationships existed between GA and CL(mf) or CL(mo). Concomitant with this was a decrease in fetal DPHM plasma unbound fraction with GA, with no such change being evident in the mother. Both CL(mo) and CL(fo) were related to the respective DPHM plasma unbound fraction. A strong relationship also existed between fetal plasma unbound fraction and CL(fm). Thus, the decrease in fetal unbound fraction of DPHM during gestation could contribute to the fall in CL(fm), and possibly CL(fo). However, over the GA range studied, fetal DPHM free fraction decreased by approximately 47%, whereas CL(fm) fell by approximately 66%. Because fetal unbound fraction and CL(fm) are linearly related, the GA-associated fall in unbound fraction appears to be insufficient to account for the entire decline in CL(fm). In separate studies in pregnant sheep, we observed a approximately 40% fall in weight-normalized Q(um) between 125 and 137 days' gestation. Because CL(fm) for DPHM is similar to that of flow-limited compounds (e.g., ethanol, antipyrine), this decrease in Q(um) may also contribute to the GA-related fall in CL(fm).
Amphotericin B both inhibits and enhances T-cell proliferation: inhibitory effect is mediated through H(2)O(2) production via cyclooxygenase pathway by macrophages.
Amphotericin B (AmB) has been shown to have both immunosuppressive and -enhancing effects, making its precise nature of action enigmatic. In the present study, we found that AmB inhibited concanavalin A (Con A)-induced T cell proliferation if added within first 30 min of stimulation, after which inhibition began to diminish rapidly. However, AmB did not inhibit T-cell proliferation induced by a combination of PMA and ionomycin. AmB inhibition of Con A-induced proliferation was completely overcome by cyclooxygenase inhibitor ibuprofen ([alpha-methyl-4-(isobutyl)phenylacetic acid]) and H(2)O(2) scavenger catalase. In fact, in the presence of ibuprofen and catalase, AmB enhanced, instead of suppressing, Con A-induced proliferation in a dose-dependent way. The effect of catalase was limited to the removal of extracellular H(2)O(2) only, as the enzyme did not enter the cells. AmB stimulated H(2)O(2) production by macrophages, but not by a lymphocyte population, which was inhibited by ibuprofen. Our T-cell preparation contained about 3% macrophages, and AmB inhibition of proliferation was further pronounced by increasing the macrophage number by as little as 1%. Finally, AmB inhibition of Con A-induced T-cell proliferation was completely overcome by 2-mercaptoethanol. On the basis of these results, we suggest that AmB stimulates H(2)O(2) production by macrophages through the activation of the cyclooxygenase pathway of arachidonate metabolism. H(2)O(2) then inhibits Con A-induced T-cell proliferation by interfering with an early step of the T-cell receptor signaling pathway through the oxidative modification of some signaling proteins. Our results also show that AmB enhances T-cell proliferation, which can be seen only after blocking its inhibitory effect.
Three-dimensional real-time magnetic resonance-guided interstitial prostate brachytherapy optimizes radiation dose distribution resulting in a favorable acute side effect profile in patients with clinically localized prostate cancer.
PURPOSE: A large number of men are diagnosed with early-stage prostate cancer as a result of prostate-specific antigen (PSA) screening. For many of these men, prostatectomy results in long-term freedom from biochemical and clinical failure. Despite limited follow-up data, ultrasound-guided prostate brachytherapy has gained acceptance as a treatment for early-stage prostate cancer, in part due to its favorable side effect profile and brief recovery period. We report on the use of three-dimensional real-time magnetic resonance (MR) guidance, which has several advantages compared with biplanar ultrasound guidance for prostate brachytherapy, including enhanced geometric and dosimetric feedback during the procedure. MATERIALS AND METHODS: Median clinical target volume coverage of 96% was achieved using MR guidance. The ability to define more precisely the clinical target volume with MR and the use of real-time assessment of dose distribution resulted in an excellent acute side effect profile. Only 19% of patients required oral alpha1 blockers for postimplant urethritis and 9% required temporary reinsertion of the Foley catheter due to acute urinary obstruction. CONCLUSIONS: These results compare favorably to those of ultrasound-guided brachytherapy. Further follow-up is needed to ascertain the impact this technique will have on cancer control and long-term quality of life.
Diacylglycerol mediates the T-cell receptor-driven Ca(2+) influx in T cells by a novel mechanism independent of protein kinase C activation.
The mechanism of Ca(2+) influx in nonexcitable cells is not known yet. According to the capacitative hypothesis, Ca(2+) influx is triggered by IP(3)-mediated Ca(2+) release from the intracellular Ca(2+) stores. Conversely, many workers have reported a lack of association between release and influx. In this work, the role of diacylglycerol (DAG) as the mediator of T-cell receptor (TCR)-driven Ca(2+) influx in T cells was investigated. Stimulation of mouse splenic T cells with naturally occurring DAG caused Ca(2+) entry in a dose- and time-dependent manner. Such stimulation was blocked by Ni(2+), a divalent cation known to block Ca(2+) channels. Inhibition of protein kinase C (PKC) by calphostin C did not inhibit, but slightly enhanced, the DAG-stimulated Ca(2+) entry. However, inhibition of DAG metabolism by DAG kinase and lipase inhibitors enhanced the DAG-stimulated Ca(2+) entry. DAG lipase and kinase inhibitors also enhanced the Ca(2+) entry in T cells stimulated through TCR/CD3 complex with anti-CD3 antibody. Calphostin C did not affect the anti-CD3-stimulated Ca(2+) entry. These results showed that TCR-driven Ca(2+) influx in T cells is mediated by DAG through a novel mechanism(s) independent of PKC activation.
'Fast track' carotid duplex scanning in a district general hospital.
UNLABELLED: 'Fast track' carotid scanning is designed to rapidly identify patients with significant symptomatic carotid stenosis and, thereby, allow prompt surgery. We review the outcome of patients referred to our open-access scanning service over 3 years and 6 months. A total of 807 cases (62% males and 38% females with a mean age of 64 years) were referred. The main presenting symptoms were TIA in 69%, amaurosis fugax in 11% and minor CVA in 8.3%. The mean time between referral and scan was 17 days. In 80% of the cases, the scan showed no significant disease and the patients were not seen in the clinic. Significant abnormality (stenosis > 70% or occlusion) was found in 20% of the patients. Of the total, 12% were reviewed in the out-patient clinic following which no action was taken, 2% had angiography but no surgery, while 5% had angiography and surgery. 1% were lost to follow-up. The mean delay from scan to operation was 36 days. CONCLUSION: Fast track scanning has led to early detection of surgically relevant carotid lesions and avoidance of delay in surgical intervention. It is an efficient and cost-effective practice.
Disposition of valproic acid in maternal, fetal, and newborn sheep. I: placental transfer, plasma protein binding, and clearance.
Separate 24-h maternal and fetal infusions of valproic acid (VPA) were administered to five pregnant sheep at 125 to 138 days gestation (term approximately 145 days) to determine maternal-fetal disposition. The pharmacokinetics of VPA were also investigated in five newborn 1-day-old lambs after a 6-h drug infusion. Plasma, urine, and amniotic and fetal tracheal fluid samples were analyzed for VPA using gas chromatography-mass spectrometry. During maternal drug infusion, the average steady-state fetal/maternal unbound VPA plasma concentration ratio was 0.81 +/- 0.09. Unbound maternal-to-fetal VPA placental clearance (69.0 +/- 20.2 ml/min/kg) was similar to that in the other direction (61.9 +/- 24.2 ml/min/kg); this indicates passive placental diffusion and intermediate placental permeability of VPA in sheep. Newborn unbound VPA clearance (0.66 +/- 0.28 ml/min/kg) was much lower than in the mother (5.4 +/- 2.7 ml/min/kg) or the fetus (62.1 +/- 22.4 ml/min/kg), and exhibited pronounced Michaelis-Menten characteristics. The elimination half-life of the drug was much longer in the newborn (18.6 +/- 2.6 h) relative to the mother (5.6 +/- 1.4 h) and the fetus (4.6 +/- 1.9 h). Thus, VPA elimination in newborn lambs is much slower as compared with adult sheep, a situation similar to that in humans. Plasma protein binding of VPA was saturable, with similar VPA binding capacities and affinities in maternal and fetal plasma. VPA was extensively displaced from binding sites in the newborn lamb during the first 1 to 2 days of life, possibly because of increased plasma free fatty acid concentrations at birth. Thereafter, newborn plasma appeared to have a similar VPA binding capacity but lower affinity compared with the mother and the fetus.
Disposition of valproic acid in maternal, fetal, and newborn sheep. II: metabolism and renal elimination.
Metabolism and renal excretion of valproic acid (VPA) were examined in maternal, fetal, and newborn sheep to identify the underlying reasons for the previously observed reduced VPA clearance in newborn lambs. Plasma and urine from VPA infusion studies in maternal, fetal, and newborn sheep were analyzed for VPA and its metabolites [VPA-glucuronide; beta-oxidation products: (E)-2-ene, (E)-3-ene, and 3-keto VPA; hydroxylated metabolites: 3-hydroxy, 4-hydroxy, and 5-hydroxy VPA (5-OH VPA); and 4-ene VPA, 4-keto VPA, 2-propylglutaric acid, and 2-propylsuccinic acid] using gas chromatography-mass spectrometry. All measured metabolites were detectable in maternal and fetal plasma, with 3-keto and 5-OH VPA being at higher concentrations in the fetus. Plasma concentrations of (E)-2-ene, (E)-3-ene, 3-keto, and 5-OH VPA were higher in the newborn compared with the mother, whereas those of the other metabolites were similar. A smaller percentage of the dose was excreted as VPA-glucuronide in newborn lamb urine (28.3 +/- 12.0%) compared with the mother (77.0 +/- 7.8%). Similarly, a lower fraction of the dose was excreted unchanged in newborn urine (11.0 +/- 5.8%) relative to the urine of the mother (19.3 +/- 5.8%); however, significantly larger percentages were excreted as (E)-2-ene (0.11 +/- 0.04 versus 0.02 +/- 0.01%), 3-keto (11.6 +/- 3.5 versus 1. 6 +/- 0.8%), 4-hydroxy (6.1 +/- 3.2 versus 2.3 +/- 1.3%), and 5-OH VPA (2.2 +/- 0.6 versus. 0.8 +/- 0.6%). The major reason for the reduced VPA elimination in newborn lambs appears to be impaired renal excretion and glucuronidation capacity. As a result, a larger fraction of the dose is channeled to beta-oxidation and hydroxylation pathways. The beta-oxidation activities are high at birth; this may explain the high plasma concentrations of (E)-2-ene and 3-keto VPA observed in newborn lambs and human newborns exposed to VPA.
Temporary balloon occlusion of internal carotid artery : a simple and reliable clinical test.
Balloon test occlusion of internal carotid artery has been frequently used in preoperative evaluation of patients with carotid aneurysms, fistulas and skull based neoplasms in whom arterial sacrifice is planned or considered as a possible part of therapy. We present our experience of the test in 28 patients. The test was positive in four and negative in twenty four patients. The results are compared with cross-compression angiography and the outcome following internal carotid artery sacrifice. There were no complications related to the test and the results accurately predicted the tolerance to occlusion of artery. We found the test safe, simple to perform and reliable to preoperatively detect patients at risk of ischaemic stroke following surgical ligation or endovascular occlusion of internal carotid artery.
A case of cerebral toxoplasmosis.
A histopathologically proven case of cerebral toxoplasmosis in a young HIV positive patient has been presented. The clinical problems in management are highlighted.