Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 379 records · Page 21Linked to original sources

PubMed2000

Differential effects of SB 242235, a selective p38 mitogen-activated protein kinase inhibitor, on IL-1 treated bovine and human cartilage/chondrocyte cultures.

The p38 MAP kinase inhibitor, SB 242235, was evaluated for its effects on the metabolism of bovine and human cartilage and primary chondrocyte cultures. SB 242235 had no effect on proteoglycan synthesis (PG) in bovine articular cartilage explants (BAC), as measured by [(35)S]-sulfate incorporation into glycosaminoglycans (GAGs). In addition, the compound had no effect on IL-1 alpha-induced GAG release from these cultures. However, there was a potent, dose-dependent inhibition of nitric oxide (NO) release from IL-1 alpha-stimulated BAC with an IC(50)of approximately 0.6 microM, with similar effects observed in primary chondrocytes. The effect on BAC was time dependent, and mechanistically did not appear to be the result of inhibition of protein kinase C (PKC), protein kinase A (PKA) or MEK-1. The effect on NO release in bovine chondrocytes was at the level of inducible nitric oxide synthase (iNOS) gene expression, which was inhibited at similar concentrations as nitrite production. In primary human chondrocytes, IL-1 beta induction of p38 MAP kinase was inhibited by SB 242235 with an IC(50)of approximately 1 microM. Surprisingly, however, treatment of IL-beta-stimulated human cartilage or chondrocytes with SB 242235 did not inhibit either NO production or the induction of iNOS. On the other hand, the natural product hymenialdisine (HYM), a protein tyrosine kinase (PTK) inhibitor, inhibited NO production and iNOS in both species. In contrast to the differential control of iNOS, PGE(2)was inhibited by SB 242235 in both IL-1-stimulated bovine and human chondrocyte cultures. These studies indicate that there are species differences in the control of iNOS by p38 inhibitors and also that different pathways may control IL-1-induced proteoglycan breakdown and NO production.

Animals↗

PubMed2000

FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis.

OBJECTIVE: To characterize a novel secreted frizzled-related protein (SFRP) and determine its tissue distribution at the mRNA and protein level. METHODS: The FrzB-2 gene was identified by expressed sequence tag (EST) analysis of human tissue-derived libraries. Tissue distribution of FrzB-2 mRNA was determined by Northern blot analysis and in situ hybridization. FrzB-2 protein reactivity was localized in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody against a peptide sequence unique to FrzB-2. Apoptosis was detected in articular cartilage sections using Tunel staining. RESULTS: ESTs corresponding to FrzB-2 were found in osteoblast, chondrosarcoma, osteosarcoma, osteoclastoma and synovial fibroblast libraries. FrzB-2 mRNA is expressed in a number of tissues and cell types including bone-related cells and tissues such as primary human osteoblasts and osteoclastoma. In situ hybridization studies showed strong FrzB-2 mRNA expression in human chondrocytes in human osteoarthritic (OA) cartilage but negligible levels in normal cartilage chondrocytes. The FrzB-2 cDNA encodes a secreted 40 kDa protein consisting of 346 amino acids. FrzB-2 is 92. 5% identical to the rat orthologue, DDC-4, which has been shown to be associated with physiological apoptosis. FrzB-2 protein was selectively detected in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody. Consistent with its potential role in apoptosis, positive FrzB-2 staining and Tunel positive nuclei staining were detected in chondrocyte clones in sections of human OA cartilage. CONCLUSION: These data suggest that FrzB-2 may play a role in apoptosis and that the expression of this protein may be important in the pathogenesis of human OA.

Amino Acid Sequence↗

PubMed2000

Predicting electrodiagnostic outcome in patients with upper limb symptoms: are the history and physical examination helpful?

OBJECTIVE: To determine the effectiveness of medical history and physical examination in predicting electrodiagnostic outcome in patients with suspected cervical radiculopathy. METHODS: Data on 183 subjects prospectively collected at five different electrodiagnostic laboratories were analyzed (96 cervical radiculopathies, 45 normal studies, and 42 abnormal electrodiagnostic findings other than radiculopathy). The sensitivity, specificity, positive predictive value, negative predictive value, and odds ratios were determined for symptoms and neurologic signs. RESULTS: Symptoms of numbness, weakness, and tingling were associated with twice the probability of having abnormal electrodiagnostic study results in general, yet were not helpful in identifying a cervical radiculopathy. All single and combined physical examination components had poor sensitivities, with the exception of weakness, but much higher specificities. Patients with either weakness or reduced reflexes on physical examination were up to five times more likely to have abnormal electrodiagnostic findings. In subjects with any abnormal neurologic sign, the sensitivity improved to 84%, the positive predictive value was 79%, but the specificity was low (44%). Of those subjects with normal physical examination results, almost one half had an abnormal electrodiagnostic study result (negative predictive value 52%). CONCLUSIONS: In a population of patients with suspected cervical radiculopathy, medical history and physical examination are helpful yet not sufficient to predict the electrodiagnostic outcome.

Adolescent↗

PubMed2000

Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy.

Of 4257 patients with gestational trophoblastic disease (GTD) registered between 1986 and 1996 with the Trophoblastic Screening and Treatment Centre, Sheffield, 231 women required chemotherapy; 28 were treated 24 weeks or more after the initial evacuation of products of conception. In 18 patients late treatment was a result of a predetermined watch and wait policy on the part of the Centre; these patients formed the study group. Patients were identified from the Centre's computer database. The time interval from first evacuation (diagnosis) to start of chemotherapy was calculated for each patient. Hospital records were reviewed when the interval of observation was 24 weeks or greater to determine patient characteristics, treatment and outcome. Eighteen women were treated 'late' (according to Centre policy), with a median age of 30 years (range 21-57 years). The interval from diagnosis to treatment ranged from 24 to, in one case, 56 weeks (median 33 weeks). Fourteen of 18 women had complete moles, 3/18 had partial moles and one had unclassified disease. All women had low-risk disease and were treated with single-agent methotrexate; 17 were cured with this regimen, one also required salvage chemotherapy. In conclusion, where a successful surveillance programme is in operation for GTD, a wait and watch policy can be adopted without compromising patients whose definitive treatment is commenced more than 6 months after the initial diagnosis.

Adult↗

PubMed2000

Growing skull fracture of ethmoid: a report of two cases.

We describe a rare sequel of ethmoid fracture--a growing skull fracture associated with cerebrospinal fluid rhinorrhoea following trauma sustained in adult life. The natural history of its development, diagnosis, and the results of surgery are discussed. The literature is reviewed with regard to aetiology, incidence, imaging characteristics and management of this rare post-traumatic complication.

Adult↗

PubMed2000

Isolation of taxoids from cell suspension cultures of Taxus wallichiana.

Cell suspension cultures of stem-derived callus of Taxus wallichiana in MS-F culture media were found to produce three C-14 oxygenated taxoids and one regular taxoid. The taxoids were identified as yunnanxane (1), 2 alpha, 5 alpha, 10 beta, 14 beta-tetraacetoxy-4(20),11-taxadiene (2), 2 alpha, 5 alpha, 10 beta-triacetoxy-14 beta-(2-methyl)-butyryloxy-4(20),11-taxadiene (3) and 1 beta-hydroxybaccatin I (4).

Alkaloids↗

PubMed2000

Reduction of congenital nystagmus amplitude with auditory biofeedback.

PURPOSE: Treatment options for congenital nystagmus without null position are limited. The purpose of this study was to evaluate the role of auditory biofeedback in controlling congenital nystagmus. METHODS: Ten patients with congenital nystagmus without null position underwent 6 sessions (twice a week for 3 weeks) of auditory biofeedback. Each half-hour session had simultaneous electronystagmographic recording done during the session. RESULTS: The patients could reduce the nystagmus during the treatment sessions. Mean amplitude (degrees) of nystagmus was reduced from 6. 28 +/- 4.94 to 3.05 +/- 2.48 (P =.028) and mean intensity (amplitude x frequency) was reduced from 33.37 +/- 22.84 to 13.35 +/- 7.99 (P =. 0174), but the mean frequency change was not significant, from 5.8 +/- 1.05 to 4.98 +/- 1.35 (P =.148). The mean amplitude and mean intensity decreased by 51% and 60%, respectively. After completion of the session, although a subjective improvement was reported, the patient's binocular visual acuity on Snellen's charts and contrast sensitivity did not show any significant change. Also no sustained benefit was noted because the electronystagmographic recordings reverted to baseline after the auditory stimulus for biofeedback was discontinued. CONCLUSION: Simultaneous electronystagmographic recording shows significant reduction of nystagmus amplitude and intensity because of auditory biofeedback only during the treatment session. The beneficial effect does not persist after the auditory stimulus is discontinued. No objective effect on visual acuity and contrast sensitivity was noted after the therapy.

Acoustic Stimulation↗

PubMed2000

Effect of trunk rotation and arm position on gross upper extremity adduction strength and muscular activity.

The aim of the experiment was to determine the impact of axial trunk rotation and arm position on upper extremity adduction force and muscle activity. Ten healthy male subjects performed graded maximum voluntary contractions under isometric conditions in seven upper extremity positions and three trunk postures (neutral and 90 degrees left/right rotated) in a simulated manual materials handling task. A custom built lightweight force-measuring device was held between the palmar surfaces of the hands and subjects compressed the lateral surfaces of the device. Muscle activity was recorded bilaterally over the muscle bellies of the anterior deltoid, the long head of the biceps brachii and over the flexor carpi radialis. The activity of the right pectoralis major was also recorded unilaterally. Descriptive, multivariate analysis of variance (MANOVA) and post-hoc Scheffé comparisons were performed on the mean and peak force as well as the EMG [electromyographic] data. Further analysis was performed on the force-EMG relationship at 20% intervals of maximum voluntary contraction (force). Both upper extremity adduction force and EMG were significantly affected by position (p<0.01) but not by trunk rotation. The muscle activity increased and force decreased with flexion of the upper extremity. Pearson correlation coefficients between force and EMG were low. The biceps and flexors were the most active muscles depending upon upper extremity position, and the right pectoralis major muscle activity expressed the highest correlation with force. The present findings confirm earlier hypotheses that upper extremity adduction strength is not significantly affected by trunk rotation.

Adult↗

PubMed2000

Metabolic cost and subjective assessment of palletizing and subsequent recovery.

Twenty-one male blue collar workers repeatedly lifted (palletized) a box weighing 22 kg six times min(-1) for 5 min to a shelf of fixed height. The experimental conditions included two planes of lifting (symmetries), two shelf clearances, and three headrooms. The metabolic (heart rate, caloric cost and ventilation volume) and psychophysical variables (rate of perceived exertion, RPE; visual analogue score, VAS; and body part discomfort ratings, BPDR) were measured during resting, palletization, and recovery phases. In palletization the heart rate and metabolic cost ranged between 25 to 35% of the maximal aerobic capacity. Of the three factors only headroom had a significant effect on metabolic cost (p<0.02) and the BPDR for low back (p<0.05). In the recovery phase only headroom had significantly effect (p<0.001) on metabolic cost. The metabolic recovery took 10 min; however, recovery measured through psychophysical indices appeared to continue for 20 min.

Adult↗

PubMed2000

Isolation and characterization of a 31 kDa mycobacterial antigen from tuberculous sera and its identification with in vitro released culture filtrate antigen of mtb H37Ra bacilli.

Antigens released in vivo are of considerable interest in the immunodiagnosis of infectious diseases. Circulating antigen was isolated from bacteriologically confirmed tuberculous sera by ammonium sulphate precipitation. The protein fraction between 36%, and 75%, ammonium sulphate was reactive with tuberculosis (TB) sera showing the presence of circulating tubercular antigen (CTA). Fractionation of CTA on ultrogel AcA 34 gel filtration column gave 3 protein fractions CTA1, CTA2 and CTA3. CTA2 showed maximum antigenic activity by sandwich enzyme-linked immunosorbent assay (ELISA). SDS-PAGE fractionation and seroreactivity studies showed the presence of highly reactive tubercular antigen in CTA2-7 protein fraction by sandwich ELISA. Further fractionation of CTA2-7 on cation exchange fast-protein liquid chromatography (FPLC) gave 4 antigenic fractions, of which CTA2-7D was seroreactive similar to 31 kDa antigen (ESAS-7F) isolated from in vitro culture medium. Furthermore, CTA2-7D could inhibit binding of in vitro released ESAS-7F to affinity purified antibodies in inhibition ELISA. CTA2-7D antigen may be used as a target antigen in confirming active tubercular infection. Biochemical characterization showed circulating antigen CTA2-7D to be a lipoglycoprotein is released in vivo. ESAS-7F as a glycoprotein is released in vitro culture.

Ammonium Sulfate↗

PubMed2000

Biodegradation of alpha and beta isomers of endosulphan and endosulphan sulphate in Indian soils.

The degradation of alpha and beta isomers of endosulphan and endosulphan sulphate in four sterilized and non sterilized Indian soils under laboratory conditions was studied. Degradation was found to be more in non-sterilized as compared to the sterilized soil. The half life of alpha-endosulphan, beta-endosulphan and endosulphan sulphate was found to be 136.8, 273 and 301 days in sterilized Alfisol and 55, 256 and 277 days in non-sterilized Alfisol,respectively. Alpha-endosulphan degraded more readily than beta-endosulphan and endosulphan sulphate under both sterilized and non-sterilized soil conditions.

Biodegradation, Environmental↗

PubMed2000

HELANAL: a program to characterize helix geometry in proteins.

A detailed analysis of structural and position dependent characteristic features of helices will give a better understanding of the secondary structure formation in globular proteins. Here we describe an algorithm that quantifies the geometry of helices in proteins on the basis of their C alpha atoms alone. The Fortran program HELANAL can extract the helices from the PDB files and then characterises the overall geometry of each helix as being linear, curved or kinked, in terms of its local structural features, viz. local helical twist and rise, virtual torsion angle, local helix origins and bending angles between successive local helix axes. Even helices with large radius of curvature are unambiguously identified as being linear or curved. The program can also be used to differentiate a kinked helix and other motifs, such as helix-loop-helix or a helix-turn-helix (with a single residue linker) with the help of local bending angles. In addition to these, the program can also be used to characterise the helix start and end as well as other types of secondary structures.

Algorithms↗

PubMed2000

Real-time magnetic resonance imaging-guided brachytherapy in the treatment of selected patients with clinically localized prostate cancer.

BACKGROUND AND PURPOSE: A real-time three-dimensional magnetic resonance imaging (MRI)-guided implant technique has been designed and implemented. This report summarizes the dosimetry achieved and the acute morbidity in the first patients. PATIENTS AND METHODS: To date, 43 patients with clinical stage T(1c)N(X)M(0) prostate cancer, serum prostate specific antigen <10 ng/mL, and biopsy Gleason score no higher than 3 + 4 have been treated. The procedure was performed using an open magnet, with axial T1-weighted and fast spin echo images. The prescribed minimum radiation dose to the peripheral zone was 160 Gy. The total activity implanted ranged from 18.8 to 47.5 mCi using 43 to 120 (median 80) (125)I seeds. Dosimetric analyses were performed intraoperatively in real time for the tumor, anterior rectal wall, and prostatic urethra. RESULTS: The percent of the clinical target volume receiving the prescription dose was 89% to 99% (median 96%). Using a conservative estimate of 164 Gy, no more than 9% of the urethral volume exceeded the tolerated dose. Using an estimated tolerated dose of 82 Gy, 30% to 100% (median 68%) of the anterior rectal wall volume was within the dose limit. Thirty-nine patients voided spontaneously within 3 hours of Foley catheter discontinuation, although four patients required recatheterization for a period. No patient reported gastrointestinal or sexual dysfunction during the first postoperative month. CONCLUSION: A real-time MR-guided technique can achieve a minimum of 89% coverage of the tumor volume while maintaining the prostatic urethra and most of the anterior rectal wall below tolerance levels. Acute morbidity was minimal. Further follow-up is needed to ascertain the impact on cancer control and quality of life.

Aged↗

PubMed2000

Laparoscopic total extraperitoneal hernia repair: mesh fixation is unnecessary.

BACKGROUND: Inguinal hernia repair contributes significantly to the general surgeon's workload. Since the evolution of laparoscopic inguinal hernia repair, the total extraperitoneal (TEP) repair is the technique most commonly employed by laparoscopic surgeons. This technique involves the placement of a polypropylene mesh in the preperitoneal space. The issue of fixation of this mesh remains unresolved. Surgeons have previously fixed this mesh in place using laparoscopic stapling devices, suturing techniques, or, more recently, polycyanoacrylate adhesives. However, stapling the mesh not only increases the time and expense of the procedure but can cause specific complications such as nerve entrapment syndromes and osteitis pubis. PATIENTS AND METHODS: We report a series of 89 total extraperitoneal laparoscopic repairs in 80 consecutive patients using no means of mechanical or adhesive mesh fixation, irrespective of the size of the hernial defect. RESULTS: Follow-up revealed no increase in morbidity or hernia recurrence. CONCLUSION: Our experience suggests that mechanically fixing the mesh in the preperitoneal space is unnecessary. Not fixing the mesh avoids possible complications and is not associated with any increased risk of hernia recurrence.

Adult↗

PubMed2000

Single column discrepancy and dynamic max-mini optimizations for quickly finding the most parsimonious evolutionary trees.

MOTIVATION: In the maximum parsimony (MP) method, the tree requiring the minimum number of changes (discrepancy) to explain the given set of DNA or amino acid sequences is chosen to represent their evolutionary relationships. To find the MP tree, the branch-and-bound algorithm is normally used. For a partial phylogenetic-tree (one that has a subset of the organisms) the traditional algorithm assigns a cost equal to the discrepancy of the partial phylogenetic-tree. We propose a single column discrepancy heuristic which increases this cost by predicting a minimum additional discrepancy needed to attach the sequences yet to be added to the partial phylogenetic-tree. A dynamic Max-mini order of sequence addition is also proposed to quickly terminate branch-and-bound search paths that are guaranteed to lead to suboptimal solutions. RESULTS: We studied the running time of 47 problems generated from 17 data sets. The use of single column discrepancy heuristic speeded up the computation to 2.4-fold for static and 18.2-fold for dynamic search order. The improvement appeared to increase exponentially with the number of sequences. The proposed strategies are also likely to be useful in speeding up the MP tree search using heuristic searches that are based on branch-and-bound-like algorithms. CONTACT: s.kumar@asu.edu

Amino Acids↗

PubMed2000

Tumorigenicity of four optically active bay-region 3,4-diol 1, 2-epoxides and other derivatives of the nitrogen heterocycle dibenz[c,h]acridine on mouse skin and in newborn mice.

The nitrogen heterocycle dibenz[c,h]acridine (DB[c,h]ACR) and the enantiomers of the diastereomeric pair of bay-region 3,4-diol 1, 2-epoxides as well as other bay-region epoxides and dihydrodiol derivatives of this hydrocarbon have been evaluated for tumorigenicity on mouse skin and in the newborn mouse. On mouse skin, a single topical application of 50 or 200 nmol of compound was followed 10 days later by twice-weekly applications of the tumor promoter 12-O:-tetradecanoylphorbol-13-acetate for 20 weeks. DB[c, h]ACR and the four optically pure, bay-region 3,4-diol-1,2-epoxide isomers all had significant tumor- initiating activity. The isomer with (1R,2S,3S,4R) absolute configuration [(+)-DE-2] was the most active diol epoxide isomer. The (-)-(3R,4R)-dihydrodiol of DB[c, h]ACR, the expected metabolic precursor of the bay-region (+)-DE-2, was 4- to 6-fold more tumorigenic than its corresponding (+)-enantiomer. In tumorigenicity studies in newborn mice, a total dose of 70-175 nmol of DB[c,h]ACR or one of its derivatives was injected i.p. on days 1, 8 and 15 of life, and tumorigenic activity was determined when the mice were 36-39 weeks old. DB[c,h]ACR produced a significant number of pulmonary tumors and also produced hepatic tumors in male mice. Of the four optically active bay-region diol epoxides, only (+)-DE-2 and (+)-DE-1 with (1R,2S,3S,4R) and (1S, 2R,3S,4R) absolute configuration, respectively, produced a significant tumor incidence. At an equivalent dose, the (+)-DE-2 isomer produced several-fold more pulmonary tumors and hepatic tumors than the (+)-DE-1 isomer. The (-)-(3R,4R)-dihydrodiol, metabolic precursor of the bay-region (+)-DE-2, was strongly active and induced an equal number of pulmonary and hepatic tumors as did DB[c,h]ACR. The (+)-(3S,4S) dihydrodiol was less active. The bay-region (+)-(1R,2S)-epoxide of 1,2,3,4-tetrahydro DB[c,h]ACR was strongly tumorigenic in newborn mice whereas its (-)-(1S, 2R)-enantiomer was inactive. This contrasts with the data on mouse skin where both enantiomers had substantial tumorigenic activity. In summary, the bay-region (+)-(1R,2S,3S,4R)-3,4-diol 1,2-epoxide of DB[c,h]ACR was the most tumorigenic of the four optically active bay-region diol epoxides of DB[c,h]ACR on mouse skin and in the newborn mouse. These results with a nitrogen heterocycle are similar to earlier data indicating high tumorigenic activity for the R,S,S,R bay-region diol epoxides of several carbocyclic polycyclic aromatic hydrocarbons.

Acridines↗

PubMed2000

Expansion and molecular evolution of the interferon-induced 2'-5' oligoadenylate synthetase gene family.

The mammalian 2'-5' oligoadenylate synthetases (2'-5'OASs) are enzymes that are crucial in the interferon-induced antiviral response. They catalyze the polymerization of ATP into 2'-5'-linked oligoadenylates which activate a constitutively expressed latent endonuclease, RNaseL, to block viral replication at the level of mRNA degradation. A molecular evolutionary analysis of available OAS sequences suggests that the vertebrate genes are members of a multigene family with its roots in the early history of tetrapods. The modern mammalian 2'-5'OAS genes underwent successive gene duplication events resulting in three size classes of enzymes, containing one, two, or three homologous domains. Expansion of the OAS gene family occurred by whole-gene duplications to increase gene content and by domain couplings to produce the multidomain genes. Evolutionary analyses show that the 2'-5'OAS genes in rodents underwent gene duplications as recently as 11 MYA and predict the existence of additional undiscovered OAS genes in mammals.

2',5'-Oligoadenylate Synthetase↗

PubMed2000

Factors enhancing protein thermostability.

Several sequence and structural factors have been proposed to contribute toward greater stability of thermophilic proteins. Here we present a statistical examination of structural and sequence parameters in representatives of 18 non-redundant families of thermophilic and mesophilic proteins. Our aim was to look for systematic differences among thermophilic and mesophilic proteins across the families. We observe that both thermophilic and mesophilic proteins have similar hydrophobicities, compactness, oligomeric states, polar and non-polar contribution to surface areas, main-chain and side-chain hydrogen bonds. Insertions/deletions and proline substitutions do not show consistent trends between the thermophilic and mesophilic members of the families. On the other hand, salt bridges and side chain-side chain hydrogen bonds increase in the majority of the thermophilic proteins. Additionally, comparisons of the sequences of the thermophile-mesophile homologous protein pairs indicate that Arg and Tyr are significantly more frequent, while Cys and Ser are less frequent in thermophilic proteins. Thermophiles both have a larger fraction of their residues in the alpha-helical conformation, and they avoid Pro in their alpha-helices to a greater extent than the mesophiles. These results indicate that thermostable proteins adapt dual strategies to withstand high temperatures. Our intention has been to explore factors contributing to the stability of proteins from thermophiles with respect to the melting temperatures (T(m)), the best descriptor of thermal stability. Unfortunately, T(m) values are available only for a few proteins in our high resolution dataset. Currently, this limits our ability to examine correlations in a meaningful way.

Animals↗