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Biomedical subjects

V Ramakrishnan

Publications and source records attributed to V Ramakrishnan.

At least 55 records · Page 3Linked to original sources

V-Y advancement flap and composite graft for alar-groove reconstruction.

A one-stage procedure combining a V-Y advancement flap with a composite graft for the reconstruction of alar-lobule and alar-groove defects is described. After tumour resection, a V-Y flap is advanced and retained at the level of the piriform margin to fill the dead space. To provide vascular support to the composite graft and to recreate the alar groove the advancing edge of the flap is de-epithelialised. In the same stage the composite graft is harvested and placed into the alar defect. A series of 12 patients underwent this procedure, with good results.

Aged↗

Lymphoedema of the eyelids.

Lymphoedema of the eyelids interfering with vision can be a very debilitating condition. The aetiology is frequently unknown. Successful treatment by debulking and skin grafting has been described in a few cases. We present a case of sudden onset of massive bilateral eyelid oedema, which was treated using staged debulking without skin grafting. However, the cosmetic result was poor in comparison with skin grafting, suggesting that skin grafting may be a better way of treating this difficult problem.

Blepharoplasty↗

Reconstruction of the natal cleft with a perforator-based flap.

Recurrent chronic conditions of the natal cleft, such as pilonidal sinuses, are difficult problems to treat. The deep natal cleft and the rolling effect of one buttock surface over the other contribute to the high recurrence rate. Wide excision of the affected area is the treatment of choice; to cover the defect many techniques have been described that flatten the natal cleft and shift the suture line away from the midline to try to reduce recurrence. These techniques include Z-plasties, rhomboid flaps, V-Y flaps, gluteus maximus myocutaneous flaps and others. Five patients with recurrent natal-cleft problems were operated on over a 1 year period. After wide excision of the natal cleft, the defect was reconstructed with a parasacral perforator-based flap. Preoperatively, a perforator situated superolaterally to the defect is identified with a Doppler probe; the flap is then designed horizontally around the perforator and, after elevation, is rotated 908 over the defect. The mean hospital stay was 5 days. Follow-up ranged from 3 months to 15 months, with no signs of recurrence. We believe this to be a simple and reliable technique, with the advantages of placing the scars away from the midline and flattening the natal cleft - factors that help to prevent recurrence.

Adult↗

Crystal structure of the 30 S ribosomal subunit from Thermus thermophilus: purification, crystallization and structure determination.

We describe the crystallization and structure determination of the 30 S ribosomal subunit from Thermus thermophilus. Previous reports of crystals that diffracted to 10 A resolution were used as a starting point to improve the quality of the diffraction. Eventually, ideas such as the addition of substrates or factors to eliminate conformational heterogeneity proved less important than attention to detail in yielding crystals that diffracted beyond 3 A resolution. Despite improvements in technology and methodology in the last decade, the structure determination of the 30 S subunit presented some very challenging technical problems because of the size of the asymmetric unit, crystal variability and sensitivity to radiation damage. Some steps that were useful for determination of the atomic structure were: the use of anomalous scattering from the LIII edges of osmium and lutetium to obtain the necessary phasing signal; the use of tunable, third-generation synchrotron sources to obtain data of reasonable quality at high resolution; collection of derivative data precisely about a mirror plane to preserve small anomalous differences between Bijvoet mates despite extensive radiation damage and multi-crystal scaling; the pre-screening of crystals to ensure quality, isomorphism and the efficient use of scarce third-generation synchrotron time; pre-incubation of crystals in cobalt hexaammine to ensure isomorphism with other derivatives; and finally, the placement of proteins whose structures had been previously solved in isolation, in conjunction with biochemical data on protein-RNA interactions, to map out the architecture of the 30 S subunit prior to the construction of a detailed atomic-resolution model.

Crystallization↗

Increased thrombogenesis and embolus formation in mice lacking glycoprotein V.

The glycoprotein (GP) Ib-V-IX complex plays a critical role in initiating platelet adhesion to von Willebrand factor (vWF) at the site of vascular injury. The complex also forms a high-affinity binding site for thrombin. Using an intravital microscopy mouse model, it was previously established that vWF plays a critical role in mediating platelet adhesion and thrombus formation following mesenteric arteriolar injury induced by ferric chloride. Further characterization of this model showed that these thrombotic events were also thrombin dependent. Using this vWF- and thrombin-dependent model, this study shows that GP V gene deficiency significantly accelerates both platelet adhesion and thrombus formation in mice following arteriolar injury. The time required for vessel occlusion in GP V-deficient (GP V(-/-)) mice was significantly shorter than that in wild-type mice. Interestingly, large emboli were also produced in GP V(-/-) mice, but not in wild-type mice, causing frequent downstream occlusion. However, when the 2 genotypes were compared in the in vitro perfusion chamber where thrombin was inhibited by heparin, no significant differences were found in either initial single-platelet adhesion or thrombus volume. These results demonstrate that GP V(-/-) mice have accelerated thrombus growth in response to vascular injury and suggest that this is caused by enhanced thrombin-induced platelet activation rather than enhanced binding of GPIb-V-IX to vWF. Absence of GP V also compromises thrombus stability.

Animals↗

Recognition of cognate transfer RNA by the 30S ribosomal subunit.

Crystal structures of the 30S ribosomal subunit in complex with messenger RNA and cognate transfer RNA in the A site, both in the presence and absence of the antibiotic paromomycin, have been solved at between 3.1 and 3.3 angstroms resolution. Cognate transfer RNA (tRNA) binding induces global domain movements of the 30S subunit and changes in the conformation of the universally conserved and essential bases A1492, A1493, and G530 of 16S RNA. These bases interact intimately with the minor groove of the first two base pairs between the codon and anticodon, thus sensing Watson-Crick base-pairing geometry and discriminating against near-cognate tRNA. The third, or "wobble," position of the codon is free to accommodate certain noncanonical base pairs. By partially inducing these structural changes, paromomycin facilitates binding of near-cognate tRNAs.

Anti-Bacterial Agents↗

Calcite precipitation induced by polyurethane-immobilized Bacillus pasteurii.

Polyurethane (PU) foam was used to immobilize the whole cell of Bacillus pasteurii. The immobilized cells exhibited the rates of calcite precipitation and ammonia production as high as those of the free cells. Scanning electron micrographs identified the cells embedded in calcite crystals throughout PU matrices. Calcite in PU showed little effect on the elastic modulus and tensile strength of the polymer, but increased the compressive strengths of concrete cubes, whose cracks were remediated with PU-immobilized cells. These observations led us to believe that the calcite might remain as a form of precipitation, not as a bonding material within the matrices.

Journal Article↗

A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V.

Glycoprotein (GP) V is a major substrate cleaved by the protease thrombin during thrombin-induced platelet activation. Previous analysis of platelets from GP V-null mice suggested a role for GP V as a negative modulator of platelet activation by thrombin. We now report the mechanism by which thrombin activates GP V -/- platelets. We show that proteolytically inactive forms of thrombin induce robust stimulatory responses in GP V null mouse platelets, via the platelet GP Ib--IX--V complex. Because proteolytically inactive thrombin can activate wild-type mouse and human platelets after treatment with thrombin to cleave GP V, this mechanism is involved in thrombin-induced platelet aggregation. Platelet activation through GP Ib-IX depends on ADP secretion, and specific inhibitors demonstrate that the recently cloned P2Y(12) ADP receptor (G(i)-coupled ADP receptor) is involved in this pathway, and that the P2Y(1) receptor (G(q)-coupled ADP receptor) may play a less significant role. Thrombosis was generated in GP V null mice only in response to catalytically inactive thrombin, whereas thrombosis occurred in both genotypes (wild type and GP V null) in response to active thrombin. These data support a thrombin receptor function for the platelet membrane GP Ib--IX--V complex, and describe a novel thrombin signaling mechanism involving an initiating proteolytic event followed by stimulation of the GP Ib--IX via thrombin acting as a ligand, resulting in platelet activation.

Animals↗

Crystal structure of an initiation factor bound to the 30S ribosomal subunit.

Initiation of translation at the correct position on messenger RNA is essential for accurate protein synthesis. In prokaryotes, this process requires three initiation factors: IF1, IF2, and IF3. Here we report the crystal structure of a complex of IF1 and the 30S ribosomal subunit. Binding of IF1 occludes the ribosomal A site and flips out the functionally important bases A1492 and A1493 from helix 44 of 16S RNA, burying them in pockets in IF1. The binding of IF1 causes long-range changes in the conformation of H44 and leads to movement of the domains of 30S with respect to each other. The structure explains how localized changes at the ribosomal A site lead to global alterations in the conformation of the 30S subunit.

Base Pairing↗

Identification of the platelet ADP receptor targeted by antithrombotic drugs.

Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

Adenosine Diphosphate↗

Video microsurgery: early experience with an alternative operating magnification system.

Since Nylen first used an operating microscope in 1921, its basic design has remained fundamentally unchanged. Microsurgical procedures are still performed while viewing the subject through binocular eyepieces. This article examines the potential to perform microsurgery using video technology, operating with a television monitor. The development of the videomicroscope is discussed together with its early trials. The results show the potential to perform simple microsurgical procedures while viewing the procedure in a two-dimensional format. The advantages and disadvantages of such a system are discussed, together with future implications.

Humans↗

Atomic structures at last: the ribosome in 2000.

Last year, atomic structures of the 50S ribosomal subunit from Haloarcula marismortui and of the 30S ribosomal subunit from Thermus thermophilus were published. A year before that, a 7.8 A resolution electron density map of the 70S ribosome from T. thermophilus appeared. This information is revolutionizing our understanding of protein synthesis.

Binding Sites↗

Prevalence of asthma and other allergic diseases in an adolescent population: association with gender and race.

OBJECTIVES: To estimate the prevalence and severity of asthma in an adolescent population by sex and race. METHODS: Cross-sectional, population-based survey of school children. SETTING: Midwestern city experiencing damage from the 1993 Mississippi River flood. PARTICIPANTS: 2,693 children attending grades 7 to 12. MEASUREMENTS: Questions from the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: Two thousand six hundred ninety-three children were surveyed, for a response rate of 90%. In this population, 16.4% reported having ever been diagnosed with asthma; 25% reported wheezing in the last 12 months; 32% reported symptoms of rhinitis in the last 12 months; and 22% reported ever having hay fever. The prevalence rate for current asthma was 12.6%. Female students had significantly greater prevalence rates for current asthma (16.4% vs 9.0%, OR = 1.85); ever-diagnosed asthma (18.5% vs 14.3%, OR = 1.36); wheezing > or = 4 times in the last 12 months (12.0% vs 5.6%, OR = 1.95); current rhinitis (38.7% vs 25.4%, OR = 1.73); and hay fever (26.4% vs 18.4%, OR = 1.57). All associations with sex remained significant, except ever-diagnosed asthma, after controlling for other known risk factors in logistic regression. African-Americans had higher prevalence rates than other races with differences reaching statistical significance for ever-diagnosed asthma and current asthma; however, these relationships did not remain significant after controlling for other known risk factors in logistic regression. CONCLUSIONS: Our prevalence rates were similar to those reported by other studies that used the ISAAC questionnaire. Female students reported significantly more asthma, wheezing, rhinitis, and hay fever than male students. Female students also reported more severe symptoms and a greater number of emergency room and hospital admissions.

Adolescent↗

Vibrational spectroscopic study of DL-methionine dihydrogen phosphate.

The two methionine cations in the asymmetric part of the unit cell of bis(DL-methionine dihydrogen phosphate) have different conformations. This, together with the different environments seen by the two -CH2- groups in each skeleton cause several of the group wavenumbers to occur as doublets or as broad bands. The anion contains two dissimilar P-O bonds, which distorts the phosphate tetrahedron. Due to this, the stretching wavenumbers appear as doublets. There is extensive hydrogen bonding in the system in all three crystallographic directions and this is responsible for the changes in the position and intensity of several bands. Fermi resonance has also been observed.

Humans↗

Vibrational studies of [Ni(II)(DIARS)2X]X, (DIARS=o-C6H4(As(CH3)2)2 and X=Cl, Br, I).

Infrared and laser Raman spectra of [Ni(II)(diars)2X]X, (X=Cl, Br and I) have been used as probes to determine the structures of chelated diarsine molecules. It has been observed that the effects of metal chelation and coordination geometry give rise to frequency shifts in these complexes. The variation in vibrational spectroscopic features indicates reduction in the symmetry of the complexes in the crystalline environment. The effect of halogen on the Ni-halogen stretching frequency of these square pyramidal complexes is not as significant as observed in the case of octahedral complexes.

Arsenic↗

The aesthetic implication of scar position in breast reconstruction.

In these enlightened times of patient involvement in operative planning, the patient has a much greater input into procedure selection, especially where several options are available. Breast reconstruction is a prime example of combined decision making, although options are still limited by pre-existing scars and previous treatment. In this study we eliminated all variables of reconstruction except the resulting scar pattern in an attempt to discover what was most acceptable to the patient. Various postoperative results, such as single scars and flaps, were mimicked unilaterally and bilaterally by drawing them on the same live subject. These photographic images were then formulated into a questionnaire and distributed to various female groups for scoring. Results show a preference for single-line horizontal scars in unilateral and bilateral reconstructions; scars that encroached the upper medial quadrant scored less well. The preferred flap reconstruction is also positioned horizontally, but in the lower pole. Overall, the preferred reconstruction in all groups was a single unilateral horizontal scar.

Adolescent↗