Biomedical subjects
Publications and source records attributed to S Kumar.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
Di-O-glycinoyl curcumin (I), di-O-glycinoyl-C4-glycyl-curcumin (II), 5'-deoxy-5'-curcuminyl thymidine (5'-cur-T) (III) and 2'-deoxy-2'-curcuminyl uridine (2'-cur-U) (IV) have been synthesized and characeterised by elemental analysis & 1H NMR. The antibacterial activities of these four bioconjugates has been tested particularly for multiresistant micro-organisms. Best results are shown by I & IV. These bioconjugates serve dual purpose of systemic delivery as well as therapeutic agents against viral diseases.
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.
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.
CD105 (endoglin), a receptor for transforming growth factor beta (TGFbeta), is highly expressed in tissue-cultured, activated endothelial cells in vitro and in tissues undergoing angiogenesis in vivo. The absence of CD105 in knockout mice leads to their death from defective vascular development, but the role of CD105 in the modulation of angiogenesis has not been elucidated. TGFbeta1 is a well-recognized regulator of angiogenesis. Using an antisense approach, we have shown that inhibition of CD105 protein translation in cultured human endothelial cells enhances the ability of TGFbeta1 to suppress growth and migration in these cells. The ability of endothelial cells to form capillary tubes was evaluated by the use of a 3-dimensional collagen matrix system where TGFbeta1 not only reduced the length of capillary-like structures, but also caused massive mortality in CD105-deficient cells compared to control cultures. These results provide direct evidence that CD105 antagonizes the inhibitory effects of TGFbeta1 on human vascular endothelial cells and that normal cellular levels of CD105 are required for the formation of new blood vessels.
Inflammatory bowel disease (IBD) is associated with an increased risk of lymphoma, which is usually extraintestinal but sometimes may involve the diseased bowel itself. Most lymphomas described in this setting are of non-Hodgkin's type, but rare cases of Hodgkin's disease (HD) have been reported. We describe the clinicopathologic and molecular features of four patients with primary gastrointestinal HD. Three patients had preexistent Crohn's disease (CD), for which two of them had received immunosuppressive therapy. The fourth patient had a longstanding history of diverticulitis and myasthenia gravis and was receiving immunosuppressive therapy for the latter. Multifocal involvement of the bowel by HD was noted in all four cases. Disease was staged as IVA in one patient, IIIB in one patient, and IE in one patient, and the fourth patient died in the postoperative period before further workup. Two patients received chemotherapy, one of whom was dead at 9 months, whereas the other has no evidence of disease at 25 months' follow-up. The patient with IE disease did not receive any therapy because only a few microscopic foci of disease were present and is also without any evidence of disease at 17 months. The Reed-Sternberg (RS) cells in all four cases expressed CD30, CD15, EBER-1, and LMP-1; two of four were focally CD20-positive. VJ-polymerase chain reaction for immunoglobulin heavy chain (IgH) rearrangement showed a polyclonal pattern in all four cases. In two cases, laser capture microdissection was used to isolate individual RS and Hodgkin's cells, which contained rearranged immunoglobulin genes, confirming a B-cell genotype. Whereas one case showed a dominant clonal band present in all isolates, cells from the patient with stage IE disease clearly showed a polyclonal population of RS cells. Our findings indicate that HD arising in the setting of IBD or chronic inflammation is the result of an Epstein-Barr virus-driven lymphoproliferation, analogous to that found in other immunodeficient states. Disordered immunoregulation inherent to CD and immunosuppressive therapy for the latter may contribute to its development. The finding of polyclonal RS cells in a patient with early stage disease and apparent cure by surgical resection versus monoclonal RS cells in the patient with disseminated disease suggests that HD in the setting of immunodeficiency also may show molecular progression, in a manner similar to that occurring in conventional B-cell lymphoproliferative disorders arising in the same setting.
Afferent loop syndrome is caused by intermittent mechanical obstruction of the afferent loop of a gastrojejunostomy and may present early as an acute type or late as a chronic type. The authors describe two patients who were examined for a history of bilious vomiting after gastrojejunostomy, and who were thought to have afferent loop syndrome (chronic type) based on clinical findings. Results of routine investigations, such as upper gastrointestinal endoscopy, and ultrasonography were inconclusive. Findings from the barium meal follow-through studies were normal in the first patient and revealed a dilated duodenum in the second patient. Tc-99m bromotriethyl-iminodiacetic acid has been used to identify afferent loop obstruction as represented in these studies.
BACKGROUND: A prospective, randomized controlled trial was used to compare the efficacy of the arteriovenous (AV) impulse system and aspirin in reducing venous thrombosis after fracture to the femoral neck. METHODS: A total of 143 patients underwent hemiarthroplasty, after which 70 patients were treated with the AV pump and a second group of 73 patients were commenced on 325 mg of aspirin. Duplex ultrasound was used to assess both proximal and distal venous thrombi on days 7 to 10. Calf and thigh circumferences were also measured. RESULTS: Thrombi developed in seven of the patients treated with aspirin and in four patients treated with the AV pump. No statistically significant difference could be established (p = 0.109). There was a significant reduction in both calf (p = 0.003) and thigh (p = 0.002) swelling in the group treated with the AV pump. Neither treatment group was a significant predictor of a poorer outcome by using logistical regression analysis (p = 0.258). CONCLUSIONS: Both aspirin and the AV pump are effective in reducing thromboembolic events after hemiarthroplasty of the hip.