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Biomedical subjects

K Shankar

Publications and source records attributed to K Shankar.

18 recordsLinked to original sources
PubMed2001

Towards NeuroML: model description methods for collaborative modelling in neuroscience.

Biological nervous systems and the mechanisms underlying their operation exhibit astonishing complexity. Computational models of these systems have been correspondingly complex. As these models become ever more sophisticated, they become increasingly difficult to define, comprehend, manage and communicate. Consequently, for scientific understanding of biological nervous systems to progress, it is crucial for modellers to have software tools that support discussion, development and exchange of computational models. We describe methodologies that focus on these tasks, improving the ability of neuroscientists to engage in the modelling process. We report our findings on the requirements for these tools and discuss the use of declarative forms of model description--equivalent to object-oriented classes and database schema--which we call templates. We introduce NeuroML, a mark-up language for the neurosciences which is defined syntactically using templates, and its specific component intended as a common format for communication between modelling-related tools. Finally, we propose a template hierarchy for this modelling component of NeuroML, sufficient for describing models ranging in structural levels from neuron cell membranes to neural networks. These templates support both a framework for user-level interaction with models, and a high-performance framework for efficient simulation of the models.

Animals↗
PubMed2001

Diallyl sulfide inhibition of CYP2E1 does not rescue diabetic rats from thioacetamide-induced mortality.

Previously we have shown that hepatotoxicity of thioacetamide (TA) was increased in streptozotocin (STZ)-induced diabetic (DB) rats due to combined effects of enhanced bioactivation-based liver injury of TA and compromised liver tissue repair response. We have also shown that TA is primarily bioactivated by hepatic CYP2E1. The present study was done to further investigate the importance of liver tissue repair in determining the final outcome of hepatotoxicity. STZ-induced DB rats were pretreated with a CYP2E1 inhibitor, diallyl sulfide (DAS), to decrease the bioactivation-based liver injury of TA. The treatments were as follows: DB/DAS/TA, DB/corn oil/TA, and DB/DAS/saline. Nondiabetic (non-DB) rats received the same treatments as controls. A dose of TA (300 mg/kg ip), which was nonlethal in non-DB rats, caused 92 and 90% mortality in DB/DAS/TA and DB/corn oil/TA groups, respectively. At various times (0--60 h) after treatment, liver injury was assessed by plasma alanine aminotransferase and histopathology. Cell proliferation was evaluated by [(3)H]thymidine incorporation and immunohistochemical staining of proliferating cell nuclear antigen (PCNA). In the DB/DAS/TA rats, DAS pretreatment markedly reduced the CYP2E1-dependent liver injury of TA compared to that in DB/corn oil/TA rats. However, subsequent hepatic DNA synthesis in both DB groups was inhibited approximately 50%. PCNA analysis showed a corresponding decrease in cell-cycle progression. This compromised tissue repair response in DB rats was insufficient to compensate for cell loss, resulting in progression of liver injury and culminating in high mortality in both DB groups. Furthermore, non-DB rats were pretreated with a CYP2E1 inducer, isoniazid, to increase the bioactivation-based TA liver injury equal to the liver injury observed in DB/DAS/TA rats. Despite equal injury up to 36 h following TA treatment, the tissue repair response in the non-DB rats was highly stimulated to compensate for liver injury and led to 70% survival in this group. These studies underscore the importance of adequate and timely tissue repair in compensating for liver injury and protecting from lethality.

Alanine Transaminase↗
PubMed2000

Potentiation of thioacetamide liver injury in diabetic rats is due to induced CYP2E1.

Thioacetamide (TA)-induced hepatotoxicity is potentiated in streptozotocin (STZ)-induced diabetic rats. The relative roles of CYP2E1 and FMO1 in the mechanism of TA-associated liver injury were investigated. In the STZ-induced diabetic rat, hepatic CYP2E1 protein concentration and p-nitrophenol hydroxylation were induced 8- and 5.6-fold, respectively. Pretreatment with the CYP2E1 inducer, isoniazid (INH, 250 mg/kg, i.p.) before TA (300 mg/kg, i.p.) administration significantly increased TA-associated liver injury as assessed by plasma alanine aminotransferase (ALT). Hepatic CYP2E1 expression and p-nitrophenol hydroxylation were induced 2.2- and 2. 5-fold in the INH-pretreated rat, respectively. Inhibition of CYP2E1 by diallyl sulfide (DAS, 200 mg/kg, p.o., two doses) before TA administration, decreased plasma ALT activity by 60% in the nondiabetic rat and by 75% in the diabetic rat. Abolition of microsomal p-nitrophenol hydroxylation and CCl(4)-induced liver injury confirmed that hepatic CYP2E1 was highly inhibited by DAS. Hepatic flavin-containing monooxygenase (FMO) form 1 expression and methimazole-dependent oxidation of thiocholine were induced 2.5- and 1.8-fold in the diabetic rat, respectively. Dietary administration of 0.25% indole-3-carbinol (I3C) for 10 days inhibited FMO1 expression and enzyme activity in both nondiabetic and diabetic rats. Paradoxically, TA-induced liver injury was increased in these I3C-pretreated rats. These findings indicate that hepatic CYP2E1 appears to be primarily involved in bioactivation of TA. In the STZ-induced diabetic rat, diabetes-induced CYP2E1 appears to be responsible for the potentiated liver injury; Even though hepatic FMO1 is induced in the diabetic rat, it is unlikely to mediate the potentiated TA hepatotoxicity.

Alanine Transaminase↗
PubMed1998

Treatment and results of partially thrombosed giant aneurysms.

Partially thrombosed giant aneurysms are one of the most difficult diseases in the neurosurgical field. We have had 18 of these cases namely, three in vertebral artery, four in basilar artery, four in internal carotid artery, five in middle cerebral artery, and two in anterior communicating artery. Nine aneurysms were clipped, two aneurysms were removed with anastomosis, two cases were treated interventionally, and five cases were treated conservatively because of serpentine and fusiform types of aneurysms in internal carotid artery bifurcation. These conservatively treated patients died due to infarction. When surgery is selected in the thrombosed giant aneurysms, the approach is the most important to secure the neck. Three-dimensional computed tomography angiography was useful to plan the strategy for surgery. If the neck is big enough for placement of a clip, arterial reconstruction is the choice. The reconstruction must be done including an adequate size of the artery because of the thick wall. If the aneurysm neck is too small to reconstruct, aneurysmectomy with anastomosis is one of the choices.

Adult↗
PubMed1997

Clinical study of 16 fully grown cerebral aneurysms.

The mechanismus of recurrence and enlargement of 16 cerebral aneurysms have been analyzed: 2 dissecting aneurysms, 6 fully grown aneurysms after neck clipping, 1 case after treatment with dome clip, 3 ruptured aneurysms that developed at the same sites and 4 cases that developed at other sites. From our investigation we concluded it was fundamentally important that the factor of the elastic lamina interna must attach in whole around the neck with precise neck clipping or adequate tight embolization involving positioning of the remaining elastica lamina interna in coil embolization.

Aortic Dissection↗
PubMed1994

Platelet serotonin uptake in duodenal ulcer patients.

Platelet serotonin uptake was measured in 10 duodenal ulcer patients and 10 controls by determining the concentration of radioactivity in platelets after incubation with tritium-labelled serotonin binoxalate. Platelet 5-HT uptake in ulcer patients (312.0 +/- 125.0 CPM/10(7) platelets) was significantly higher than that in the control group (186.0 +/- 53.0 CPM/10(7) platelets; p < 0.01). Since the kinetics of 5-HT uptake by platelets may be a reflector of enhanced serotonergic activity, this finding may have implications in future therapeutic strategies for this disease.

Adult↗
PubMed1993

Raphe of the posterior neural tube in the chick embryo: its closure and reopening as studied in living embryos with a high definition light microscope.

Chick embryos cultured on a curved substratum show a transient enlargement of the posterior neuropore (PN), mimicking the temporary delay of PN closure as seen in the curly tail (ct) mouse mutant (van Straaten et al. [1993] Development 117:1163-1172). In the present study the PN enlargement in the chick embryo was investigated further with a high definition light microscope (HDmic), allowing high resolution viewing of living embryos in vitro. The temporary PN enlargement appeared due to considerable reopening of the raphe of the posterior neural tube, which was followed by reclosure after several hours. The raphe was subsequently studied in detail. It appeared very irregular, with small zones of apposed, open and fused neural folds. During closure, these raphe features shifted posteriorly. A distinct fusion sequence between surface epithelium and neuroepithelium was not seen. During experimental reopening of the raphe in vitro, small bridges temporarily arose, broke and disappeared quickly; they likely represented the first adhesion sites between the neural folds. More prominent adhesion sites partly detached, resulting in bridging filopodia-like connections; they probably represented the first anteroposterior locations of neural fold fusion. Our observations in the living chick embryo in vitro thus show that the caudal neural tube has an irregular raphe with few adhesion sites, which can be readily reopened. As a result of the irregularity, the PN does not close zipper-like, but button-like by forming multiple closure sites.

Animals↗
PubMed1993

Sleep staging with movement-related signals.

Body movement related signals (i.e., activity due to postural changes and the ballistocardiac effort) were recorded from six normal volunteers using the static-charge-sensitive bed (SCSB). Visual sleep staging was performed on the basis of simultaneously recorded EEG, EMG and EOG signals. A statistical classification technique was used to determine if reliable sleep staging could be performed using only the SCSB signal. A classification rate of between 52% and 75% was obtained for sleep staging in the five conventional sleep stages and the awake state. These rates improved from 78% to 89% for classification between awake, REM and non-REM sleep and from 86% to 98% for awake versus asleep classification.

Adult↗
PubMed1993

Platelet serotonin kinetics in acute myocardial infarction before and after thrombolysis.

Platelet count, platelet serotonin uptake and platelet serotonin content were analysed in 21 subjects consisting of 11 patients of evolving acute myocardial infarction (AMI) and 10 matched healthy controls before and after administration of streptokinase. Platelet counts were significantly reduced in AMI with a subsequent rise following thrombolysis. Platelet 5-HT uptake was also significantly increased in AMI and following thrombolysis, it showed a trend towards normalization. Platelet 5-HT content was significantly increased in AMI with no further significant change following thrombolysis. The results suggest that platelet activation as revealed by reduced platelet count and altered platelet serotonin kinetics, occurs in AMI and this activation is inhibited following thrombolysis. Further, it is also apparent that it is not the reperfusion but the thrombolytic agent that is responsible for inhibition of platelet activation.

Blood Platelets↗
PubMed1991

Monitoring of the ballistocardiogram with the static charge sensitive bed.

The static charge sensitive bed (SCSB) consists of a sensitive movement detector embedded in a mattress. When a subject rests on the bed, a single electrical signal, containing components reflective of cardiac, respiratory, and body movement related motion, is produced. This paper describes a digital signal processing technique to separate the BCG from the SCSB signal. An evaluation of this algorithm was conducted using recordings from normal volunteers. Comparisons with simultaneously recorded reference signals indicated that the algorithm performed satisfactorily in a laboratory environment.

Algorithms↗
PubMed1990

Craniofacial alterations following electrolytic lesions of the trigeminal motor nucleus in actively growing rats.

The objective of this study was to define further the role of the trigeminal motor nucleus (TMNu) in the postnatal ontogeny of the mammalian craniofacial skeleton. To that end, 42 male Sprague-Dawley rats underwent stereotaxic surgery at 40 days of age; 21 received small electrolytic lesions to their left-side TMNu (lesioned group) while 21 had TMNu stimulation with no actual electrolytic lesion produced (sham group). Seven rats from each group were killed at 28, 56, and 84 days postoperative to analyze trigeminal motoneuron (TMNe) count, masticatory muscle weight, and osteological growth vector data. At all three time periods, lesioned animals showed significant differences 1) between the surgery and nonsurgery sides, and 2) from sham animals. However, sham animals also demonstrated significant between-side differences for medial pterygoid muscle weight (56 days), mandibular height (28 and 56 days), and mandibular length data (84 days); these data suggested that even relatively slight damage to TMNe can create morphological changes within the craniofacial complex. Snout deviation in a lesioned rat towards the opposite side from all other lesioned animals was correlated with unique damage to its pontine reticular formation; this suggested that the observed morphological alterations of the craniofacial complex may have been due not only to TMNu damage, but also to changed expressions of the masticatory central pattern generator (CPG). Morphological alterations of the craniofacial skeleton resulting from lesions to the TMNu were likely due to changed neuromuscular activity patterns of the masticatory muscles and their biomechanical effects upon bone.

Animals↗
PubMed1990

Methodologic and compliance issues in postcoronary bypass surgery subjects.

Persons who engage in preventive health behaviors may reduce the progression of coronary artery disease. The immediate objective of this pilot study was to assess adherence to behavioral lifestyle changes in patients after coronary artery bypass graft surgery by analyzing self-reported responses using objective measures. Data on adherence to diet, exercise, and smoking were collected from questionnaires completed by each subject. Carbon monoxide index, serum cholesterol, pre- and postambulatory pulse rates, and pre- and post-stair-climbing pulse rates were measured. All tests were conducted before discharge and at a one-month follow-up visit. Analysis of objective data showed a statistically significant reduction in total serum cholesterol, decreased smoking behavior, and increased ambulation from before discharge to one-month follow-up. Analyses showed that self reports of adherence to diet, activity, and smoking cessation were consistent with objective measures in at least 50% of subjects. Serial objective measures provide valuable indicators of patient adherence and assist staff in developing individually tailored patient education.

Aged↗
PubMed1990

Accessory nerve conduction in neck dissection subjects.

Evaluation of the accessory nerve and trapezius muscle was performed on eight subjects with neck dissection secondary to oropharyngeal/laryngeal cancer. The latencies and amplitudes of the upper, middle, and lower trapezius muscle in neck dissection subjects were compared to those in healthy subjects similar in age. Subjects after neck dissection showed abnormalities of evoked responses and abnormal spontaneous discharges in electromyographic studies of the upper trapezius. Future serial studies that seek prognostic indicators of shoulder dysfunction common to neck dissection patients are warranted.

Accessory Nerve↗
PubMed1987

An electrodiagnostic study in chronic alcoholic subjects.

Electrodiagnostic tests were performed on 16 alcoholic subjects and 15 age-matched controls. The tests were done to determine whether nerve conduction parameters differentiate between healthy and alcoholic subjects, and if so, which of these are most useful. Significant differences between alcoholic subjects and controls were found in the following variables: median nerve motor velocity; median nerve sensory latency, amplitude and velocity; ulnar nerve motor amplitude and velocity; ulnar nerve sensory amplitude, latency and velocity; sural nerve sensory amplitude and velocity; and peroneal motor amplitude and velocity. The combination of ulnar and sural sensory conduction velocity tests identified 85% of the chronic alcoholic subjects by stepwise discriminant analysis. Tibial nerve H-reflex latencies were either absent or prolonged in 63% of the subjects. Bilateral facial nerve amplitudes and latencies were normal. The ulnar sensory amplitude and ulnar sensory velocity inversely correlated with the duration of excessive alcohol drinking.

Adult↗
PubMed1984

Transtelephonic monitoring of a tachycardia-terminating pacemaker.

A 66-year-old female with recurrent supraventricular tachycardia which worsened progressively was treated with an implanted tachycardia-terminating pacemaker after treatment with antiarrhythmic drug therapy had failed. The pacemaker had the capacity to detect and respond to tachyarrhythmias. Reliable sensing and termination of the patients tachycardia was accomplished in over 100 inductions of the tachyarrhythmia. Use of this tachycardia-terminating pacer has given us several new insights that may be important in the care and follow-up of all pacemaker patients.

Aged↗
PubMed1981

Some new 5-substituted benzylidene-1-phenyl-3-(2'-pyridinobutan-4'-yl) thiobarbituric acids as psychopharmacological agents.

Ten substituted thiobarbiturates have been prepared in order to evaluate their anticonvulsant activity in vivo and MAO inhibitory activity in vitro. All the compounds have been found good MAO and convulsion inhibitors. 5-(4-N,N-dimethylaminobenzylidene)-1-phenyl-3-(2'-pyridinobutan-4'-yl)thiobarbi turic acid has been found to be best in both these activities.

Animals↗