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K Kumar

Publications and source records attributed to K Kumar.

At least 55 records · Page 3Linked to original sources

A prototype electrochemical chromatographic column for use with proteins.

We developed electrochemical hardware and media targeted for protein chromatography. Two types of stationary phases were investigated. The first comprised gold-plated stainless 316L beads coated with a self-assembled monolayer of 6-mercaptohexan-1-ol and was expected to behave like an ion-exchange resin in the presence of an electric field. The secondary stationary phase comprised the first stationary phase with further functionalization with immobilized heme moieties and was expected to behave like immobilized metal affinity resin. We tested apparatus with both stationary phases using ribonuclease A as a model protein and applied potentials from -0.3 to +0.3 V versus the saturated calomel electrode. Despite low binding capacities, we demonstrated that protein retention on both stationary phases could be controlled with an applied potential. The greatest extent of electromodulation was achieved with the mercaptohexanol-based ion-exchange media.

Chromatography↗

Bistability and Electrokinetic Oscillations.

Nonlinear dynamic behavior and electrokinetic oscillations have been investigated for the membrane systems (a) 0.1 N NaCl/KCl parallel Millipore filter parallel 0.01 N NaCl/KCl; (b) 0.1 N NaCl/KCl parallel Whatman Inorganic filter parallel 0.01 N NaCl/KCl; and (c) 0.1 N NaCl/KCl parallel silver-coated filter parallel 0.01 N NaCl/KCl, from the viewpoint of testing the theories for the phenomena and elucidating the mechanism. To achieve these objectives, studies on hydrodynamic permeability, electroosmotic permeability, bistability, and electrokinetic oscillations were undertaken. Relaxation time for buildup and decay of electroosmotic pressures was experimentally determined. Bistability was not observed showing that it is not a prerequisite for oscillations and nonlinear relations between (J(v))(Deltarho=0) and Deltaφ involving cubic or higher-order terms are necessary for bistability. The oscillations were studied at different current strengths. The period is found to be independent of current, while amplitude A is found to be linearly related to current I which is the bifurcation parameter. The bifurcation point occurs at approximately 0.4 mA. Studies have also been made with membranes of different pore size that show that amplitude increases with increase in pore size of the membranes. The validity of the two-variable model of Teorell was examined by comparing the experimental results with computer simulation based on parameters determined experimentally. Theory does not meet expectation and the results suggest that modification of theory is needed. The weakness of the theory has been critically examined. Copyright 1999 Academic Press.

Journal Article↗

Three-dimensional structure of ribonuclease T1 complexed with an isosteric phosphonate substrate analogue of GpU: alternate substrate binding modes and catalysis.

The X-ray crystal structure of a complex between ribonuclease T1 and guanylyl(3'-6')-6'-deoxyhomouridine (GpcU) has been determined at 2. 0 A resolution. This ligand is an isosteric analogue of the minimal RNA substrate, guanylyl(3'-5')uridine (GpU), where a methylene is substituted for the uridine 5'-oxygen atom. Two protein molecules are part of the asymmetric unit and both have a GpcU bound at the active site in the same manner. The protein-protein interface reveals an extended aromatic stack involving both guanines and three enzyme phenolic groups. A third GpcU has its guanine moiety stacked on His92 at the active site on enzyme molecule A and interacts with GpcU on molecule B in a neighboring unit via hydrogen bonding between uridine ribose 2'- and 3'-OH groups. None of the uridine moieties of the three GpcU molecules in the asymmetric unit interacts directly with the protein. GpcU-active-site interactions involve extensive hydrogen bonding of the guanine moiety at the primary recognition site and of the guanosine 2'-hydroxyl group with His40 and Glu58. On the other hand, the phosphonate group is weakly bound only by a single hydrogen bond with Tyr38, unlike ligand phosphate groups of other substrate analogues and 3'-GMP, which hydrogen-bonded with three additional active-site residues. Hydrogen bonding of the guanylyl 2'-OH group and the phosphonate moiety is essentially the same as that recently observed for a novel structure of a RNase T1-3'-GMP complex obtained immediately after in situ hydrolysis of exo-(Sp)-guanosine 2',3'-cyclophosphorothioate [Zegers et al. (1998) Nature Struct. Biol. 5, 280-283]. It is likely that GpcU at the active site represents a nonproductive binding mode for GpU [Steyaert, J., and Engleborghs (1995) Eur. J. Biochem. 233, 140-144]. The results suggest that the active site of ribonuclease T1 is adapted for optimal tight binding of both the guanylyl 2'-OH and phosphate groups (of GpU) only in the transition state for catalytic transesterification, which is stabilized by adjacent binding of the leaving nucleoside (U) group.

Aspergillus oryzae↗

The ligament augmentation device: an historical perspective.

Anterior cruciate ligament (ACL) injury is the most common ligament injury in the knee, and a significant number of patients may develop progressive instability and disability despite aggressive rehabilitation. Various materials have been used for its reconstruction. These include autografts, allografts, prosthetic ligaments, and synthetic augmentation of the biological tissue. The concept of ligament augmentation device (LAD) arose from the observation that biological grafts undergo a phase of degeneration and loss of strength before being incorporated. The LAD is meant to protect the biological graft during this vulnerable phase. However, it provokes an inflammatory reaction in the knee, and has been found to delay maturation of autogenous graft in humans. In experimental situations, the LAD has been found to share loads in a composite graft. It has also been found to be substantially stronger than the biological graft. However, in clinical situations no significant advantages have been observed with the use of LAD to augment patellar tendon or hamstring reconstruction of the chronic ACL-deficient knee or in the acute setting to augment repair of the torn ACL. There are very few reports of the use of LAD in reconstruction of the posterior cruciate ligament, and again these do not suggest any advantage in its use. Insertion of the LAD implies the introduction of a foreign material into the knee, has been associated with complications such as reactive synovitis and effusions, and may also be associated with an increased risk of infection. At present, there is no evidence that its routine use should be advocated in uncomplicated reconstructions of the ACL using biological grafts.

Absorbable Implants↗

Work as worship.

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Attitude of Health Personnel↗

Heap corrugation and hexagon formation of powder under vertical vibrations.

We report free-surface instabilities in a deep bed of fine granular material of irregular shape under vertical vibrations. At low frequency of vibration, the conical heap due to convective flow becomes unstable above a critical amplitude of vibration and acquires an azimuthal dependence which makes the heap surface corrugated. At even higher amplitude, the heap is no longer stable and splits into small heaps on a hexagonal lattice. At high frequency, we observe standing waves (stripes) at the same frequency as the driving one. The main mechanism of these instabilities can be traced back to the presence of the surrounding gas, since they vanish under vacuum conditions.

Journal Article↗

Deep brain stimulation of the ventral intermediate nucleus of the thalamus for control of tremors in Parkinson's disease and essential tremor.

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson's disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 +/- 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 +/- 8. 1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.

Aged↗

Kala-azar epidemic in Varanasi district, India.

Reports at the Sir Sunder Lal Hospital, Banaras Hindu University, of a large number of kala-azar cases from one particular village in Varanasi district, Uttar Pradesh, led us to carry out an epidemiological study of the situation using standard techniques. The overall prevalence and case fatality of the disease were 12.9% and 10.5%, respectively. A history of fever and hepatosplenomegaly was noted for all the cases. The case definition was the presence of parasites in bone marrow or splenic aspirate smears. The disease was more prevalent among adults, but occurred also among children. However, there was no clear linear relationship between the prevalence of the disease and age group. Kala-azar occurred among males and females, and its prevalence did not correlate significantly with income. Since the disease vector continues to be present in the study area, the health authorities should take strong steps to control the disease.

Adolescent↗

High temperature induced antibiotic sensitivity changes in Pseudomonas aeruginosa.

Pseudomonas aeruginosa, which was resistant to a wide variety of antibiotics, became sensitive to several of these antibiotics when grown and tested at 46 degrees C. Cell wall antibiotics such as penicillin G and ampicillin were only effective when added to cells growing at 46 degrees C prior to a temperature shift to 37 degrees C. Antibiotics which penetrate the cytoplasmic membrane to express their inhibiting action present a pattern different from those which are active against the outer cell wall. In order that these compounds be effective, the permeability of the cytoplasmic membrane must be further altered with agents such as EDTA which allow the penetration of actinomycin D. Inhibitors of protein synthesis, such as streptomycin and chloramphenicol, have increased access to their sites of action in cells grown at 46 degrees C. Cells grown at 46 degrees C have 40% less lipopolysaccharide (LPS) than cells grown at 37 degrees C and the LPS aggregates were of large molecular size in cells grown at 46 degrees C. Growth at 46 degrees C affects the permeability properties of the outer cell wall more than the permeability properties of the cytoplasmic membrane and this was due, in part, to the selective release of LPS of LPS-protein complexes at elevated growth temperatures.

Alkaline Phosphatase↗

Teaching of pathology in United States medical schools, 1996/1997 survey.

A variety of pressures to change curriculum have resulted in revision of pathology teaching in most medical schools in the United States. Responses obtained from 71% of schools on a recent survey of pathology teaching indicate the following: There are wide variations in the extent of use of various teaching modalities with resulting emergence of different teaching formats which can be categorized as "traditional," "enhanced traditional," predominantly "problem based" or "case oriented," entirely "problem based," or some form of "hybrid" of traditional and problem based. The traditional lecture and laboratory continue to be the primary modes of teaching in the vast majority (74%) of schools, however, 53% also use other approaches, eg, small group discussion, case studies, or conferences to enhance instruction. The lecture remains an important component of instruction in all major models. The form and extent of the laboratory use varies remarkably from minimal to large number of hours of instruction. The laboratory material is incorporated into small group discussion or conferences in many schools. The use of small group discussions (presently, by 79% of schools) has increased since the last survey conducted in 1986. The mean curricular time (presently 188 hours) has dropped, however, it is not easy to quantify pathology teaching in many schools with increasing integration. Instruction is entirely integrated, multidisciplinary in 28% of schools. Computer-aided instruction is used in some form to varying extents in 66% of schools, with the majority using it as a supplementary tool. There are persistent concerns about faculty time, and high student-faculty ratio.

Autopsy↗

Epidural spinal cord stimulation for treatment of chronic pain--some predictors of success. A 15-year experience.

BACKGROUND: We have used epidural spinal cord stimulation (SCS) for pain control for the past 15 years. An analysis of our series of 235 patients has clarified the value of specific prognostic parameters in the prediction of successful SCS. METHODS: Patients were followed up for periods ranging from 6 months to 15 years with a mean follow-up of 66 months. The mean age of the 150 men and 85 women in the study was 51.4 years. Indications for SCS included failed back syndrome (114 patients), peripheral vascular disease (39 patients), peripheral neuropathy (30 patients), multiple sclerosis (13 patients), reflex sympathetic dystrophy (13 patients), and other etiologies of chronic intractable pain (26 patients). RESULTS: One hundred and eighty-nine patients received permanent devices; 111 (59%) of these patients continue to receive satisfactory pain relief. Pain attributable to failed back syndrome, reflex sympathetic dystrophy, peripheral vascular disease of lower limbs, multiple sclerosis, and peripheral neuropathy responded favorably to spinal cord stimulation. In contrast, paraplegic pain, cauda equina syndrome, stump pain, phantom limb pain, and primary bone and joint disease pain did not respond as well. Cases of cauda equina injury had promising initial pain relief, but gradually declined after a few years. After long-term follow-up, 47 of the 111 successfully implanted patients were gainfully employed, compared with 22 patients before implantation. The successful patients reported improvements in daily living as well as a decrease in analgesic usage. Multipolar stimulation systems were significantly more reliable (p < 0.001) than unipolar systems. Complications included hardware malfunction, electrode displacement, infection, and tolerance. CONCLUSION: Aside from etiologies of pain syndromes as a prognostic factor, we have identified other parameters of success. In patients who have undergone previous surgical procedures, the shorter the duration of time to implantation, the greater the rate of success (p < 0.001). The diagnosis of failed back syndrome must be considered a confounding factor in our analysis. Those patients whose pain did not follow a surgical procedure had better responses to SCS than patients who had multiple surgical procedures prior to their first implant. The advent of multipolar systems has significantly improved clinical reliability over unipolar systems. Age, sex, and laterality of pain did not prove to be of significance.

Adult↗

Physician-hospital integration strategies: impact on physician involvement in hospital governance.

This study investigated the impact of three physician-hospital contractual arrangements (PHCAs)--joint ventures, management service organizations, and not-for-profit foundations--on physician involvement in hospital governance and physician-hospital relationships. Analysis of data collected from a national sample of 1,013 hospitals revealed that PHCAs generate greater physician involvement in hospital decision making and result in lower physician-hospital conflict.

Budgets↗

Focal plaque of demyelination mimicking cerebral tumor in a pediatric patient.

Focal, demyelinating lesions of the cerebrum mimicking brain tumors are a rare phenomenon, and even rarer in a pediatric population. We document the case of a 14-year-old female whose clinical, radiological and operative findings were strongly suggestive of glioma. However, histopathology revealed a demyelinating process. This case is significant as the lesion could not be distinguished from a glioma at any time in the presentation. At 41 months follow-up, the patient remains stable without further evidence of demyelination in other areas of the brain. Such a case suggests a cautious note for the pediatrician when presented with a similar patient and illustrates the importance of consideration of a demyelinating lesion in the differential diagnosis of a mass lesion in a pediatric population.

Adolescent↗

Stereotactic cyst wall disruption and aspiration of colloid cysts of the third ventricle.

BACKGROUND: Current strategies of surgical therapy for colloid cysts have been associated with low rates of initial success and high rates of morbidity, mortality and recurrence of cysts. Cyst recurrence following simple stereotactic aspiration has been hypothesized to be due to regrowth of the epithelium composing the cyst wall. METHODS: We propose a procedure involving stereotactic disruption of the colloid cyst wall with the removal of a portion of the cyst wall followed by aspiration of cyst contents as a surgical therapy for colloid cysts. RESULTS: This procedure was performed in 2 female and 3 male patients who were followed for an average of 49 months with all patients demonstrating immediate improvement of symptoms and resolution of the cyst verified with repeat computerized tomography (CT) scans. There was one incidence of recurrence in an asymptomatic patient at 75 months postoperatively. CONCLUSION: We propose that stereotactic partial cyst wall disruption and content aspiration may limit recurrence of colloid cysts, thus offering an advantage over simple stereotactic aspiration alone.

Adult↗

Microcystic adnexal carcinoma: a report of three cases.

Microcystic adnexal carcinoma is an uncommon adnexal neoplasm. It is highly aggressive locally and its importance lies in the fact that it can be easily confused with benign adnexal tumours, particularly desmoplastic trichoepithelioma, trichoadenoma and syringoma. We report three cases of microcystic adnexal carcinoma of the skin, all three being on the face: two on the lips and one on the left eyebrow. Clinically, the neoplasms were slow growing indurated nodules or plaques. Two of the cases displayed benign features on initial biopsy and their malignant potential could not be established at that stage. On subsequent review, the three neoplasms showed all the characteristic features of microcystic adnexal carcinoma as described by Goldstein et al. and the University of Virginia study. All three patients were treated by surgery in the form of wide excision. They behaved in a highly locally malignant manner with excisions being incomplete in two of the lesions, in spite of taking an adequate margin around the clinically assessable margins. The other recurred after three years in spite of a histologically proven complete excision. Two of the tumours showed infiltration into the underlying muscle with perineural spread. Wider excision in the next stage with frozen section control achieved good clearance and after a five year follow-up period all are symptom free. None of these tumours showed any evidence of distant spread.

Aged↗

Apical muscular ventricular septal defects between the left ventricle and the right ventricular infundibulum. Diagnostic and interventional considerations.

BACKGROUND: Effective transcatheter or surgical closure of apical muscular ventricular septal defects (VSDs) requires accurate delineation of variable and often complex anatomy. These defects have generally been considered as communications between the apexes of both left and right ventricles. METHODS AND RESULTS: Among 50 consecutive patients with multiple muscular VSDs referred for transcatheter device closure between October 1987 and April 1993, a subset of 10 patients (aged 7 days to 28 years) with apical muscular VSDs shared a unique set of anatomic characteristics: (1) large and often single opening in the left ventricle; (2) multiple right ventricular openings in the anterior aspect of the apical septum; and (3) separation of the right ventricular apical region into which the VSDs open from the rest of the right ventricular inflow and outflow by prominent muscle bundles. Additional analysis of the anatomy by use of echocardiography and cineangiography showed that these muscular defects were between the left ventricular apex and right ventricular infundibular apex. In 6 patients, the transcatheter devices used to create a septum in these hearts were placed in the right ventricle, straddling muscle bundles that separated the apical VSD from the rest of the right ventricular inflow and outflow, resulting in incorporation of a portion of the right ventricular infundibular apex into the physiological left ventricle. Three patients had devices placed between the apexes of the left ventricle and the infundibulum. The defect closed spontaneously within the right ventricle in 1 patient. One patient died after surgery for tetralogy of Fallot in situs inversus. The remaining 9 patients were all clinically well at the time of their most recent follow-up visit (follow-up duration, 32 +/- 11 months). This distinct type of apical VSD was identified by echocardiography in 20 of 274 patients who were followed up clinically for muscular VSDs. CONCLUSIONS: Left ventricular-infundibular apical VSDs constitute a distinct morphological type of muscular VSD that can be distinguished by echocardiography and cineangiography. In selected cases, the infundibular apex can be separated from the rest of the right ventricular inflow and outflow to eliminate flow across these defects.

Adult↗