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Biomedical subjects

V Ramesh

Publications and source records attributed to V Ramesh.

At least 217 records · Page 12Linked to original sources
PubMed1991

NMR studies of the activation of the Escherichia coli trp repressor.

The Escherichia coli trp repressor binds to the trp operator in the presence of tryptophan, thereby inhibiting tryptophan biosynthesis. Tryptophan analogues lacking the alpha-amino group act as inducers of trp operon expression. We have used one- and two-dimensional 1H-NMR spectroscopy to compare the binding to the repressor of the corepressors L-tryptophan, D-tryptophan and 5-methyl-DL-tryptophan with that of the inducer indole-3-propionic acid. We have determined the chemical shifts of the indole ring protons of the ligands when bound to the protein, principally by magnetization-transfer experiments. The chemical shifts of the indole NH and C4 protons differ between corepressors and inducer. At the same time, the pattern of intermolecular NOE between protons of the protein and those of the ligand also differ between the two classes of ligand. These two lines of evidence indicate that corepressors and inducers bind differently in the binding site, and the evidence suggests that the orientation of the indole ring in the binding site differs by approximately 180 degrees between the two kinds of ligand. This is in contrast to a previous solution study [Lane, A.N. (1986) Eur. J. Biochem. 157, 405-413], but consistent with recent X-ray crystallographic work [Lawson, C.L. & Sigler, P.B. (1988) Nature 333, 869-871]. D-Tryptophan and 5-methyltryptophan, which are more effective corepressors than L-tryptophan, bind similarly to L-tryptophan. The indole ring of D-tryptophan appears to bind in essentially the same orientation as that of the L isomer. There are, however, some differences in chemical shifts and NOE for 5-methyltryptophan, which indicate that there are significant differences between the two corepressors L-tryptophan and 5-methyltryptophan in the orientation of the indole ring within the binding site.

Bacterial Proteins↗
PubMed1991

Sequence-specific 1H NMR assignments and structural characterization of bovine seminal fluid protein PDC-109 domain b.

Sequence-specific resonance assignments for the isolated second or b domain of the bovine seminal fluid protein PDC-109 have been obtained from analysis of two-dimensional 1H NMR experiments recorded at 500 MHz. These assignments include the identification of all aromatic and most aliphatic amino acid resonances. Stereospecific assignment of resonances stemming from the Val2 CH3 gamma,gamma' groups and from seven CH beta,beta' geminal pairs has been accomplished by analysis of 3J alpha beta coupling constants in conjunction with patterns of cross-peak intensities observed in two-dimensional nuclear Overhauser effect (NOESY) spectra. Analysis of NOESY and 3J alpha NH data reveals a small antiparallel beta-sheet involving stretches containing residues 25-28 and 39-42, a cis-proline residue (Pro4), antiparallel strands consisting of residues 1-3, 5-7, and 10-13, and an aromatic cluster composed of Tyr7, Trp26, and Tyr33. The results of distance geometry and restrained molecular dynamics calculations indicate that the global fold of the PDC-109 b domain, a type II module related to those found in fibronectin, is somewhat different from that predicted by modeling the structure on the basis of homology between type II and kringle units. A shallow depression in the molecular surface which presents a solvent-exposed hydrophobic area--a potential ligand-binding site-is identified in the NMR-based models.

Amino Acid Sequence↗
PubMed1991

Comparative efficacy of drug regimens in skin tuberculosis.

Three antituberculous drug regimens have been employed to study the therapeutic response in 90 patients with any one of the commonly encountered paucibacillary forms of skin tuberculosis, namely lupus vulgaris, tuberculosis verrucosa cutis and scrofuloderma. The first two regimens contained rifampicin, isoniazid and either pyrazinamide or thiacetazone, and the third regimen had rifampicin and isoniazid only. The disease was clinically defined as localized when confined to one area and widespread when the lesions were disseminated. The observations revealed that the response of lupus vulgaris and tuberculosis verrucosa cutis was alike in all the three regimens, with the localized lesions subsiding completely after 4 months of therapy and the more extensive forms taking 5 months. Patients with scrofuloderma responded similarly to both the triple drug regimens. The discharge, sinuses and ulcers cleared in 6 months but the lymph nodes took longer to regress, up to 7 months in localized and 9 months in more widespread scrofuloderma. To obtain the same results with rifampicin and isoniazid, all patients with widespread scrofuloderma and one-third of those with localized forms had to be treated for 10 and 9 months, respectively. No serious drug side-effects, apart from giddiness with rifampicin and acneiform eruptions with thiacetazone, were encountered. No instances of relapse were noted in the 50% of patients who were followed-up for 3 1/2 years after therapy. Single-drug therapy with isoniazid for lupus vulgaris, as given in the past, is to be discouraged as it may promote the emergence of drug-resistant bacilli in those with an undetected focus of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Tuberculous infection of the male genitalia.

The extremely rare occurrence of genital tuberculosis affecting the penis, seminal vesicles, epididymides, vas deferens and Cowper's gland is described. Diagnosis was made by demonstration of fragmented acid fast bacilli in the discharge, and caseating epithelioid cell granulomata with Langhan's giant cells detected on histopathology. Response to antitubercular drugs was prompt.

Antitubercular Agents↗
PubMed1991

Constancy of central conduction delays during development in man: investigation of motor and somatosensory pathways.

1. A cross-sectional study has been performed on 457 normal subjects to determine changes in conduction delays with age in central and peripheral motor and somatosensory pathways to the upper limb. 2. Electromagnetic stimulation was used to investigate central and peripheral conduction in motor pathways from the cortex to biceps brachii and hypothenar muscles in 308 normal human subjects aged from 32 weeks gestation to 55 years. The responses were recorded in the surface electromyogram. 3. Somatosensory potentials evoked by electrical stimulation of the median nerve have been recorded at Erb's point and over the somatosensory cortex in 149 normal subjects aged from 34 weeks gestation to 52 years to determine central and peripheral somatosensory conduction delays. 4. The conduction delays in the central components of both motor and somatosensory pathways rapidly decrease over the first 2 years after birth and thereafter remain constant at adult values. 5. The conduction delays in the peripheral components of both motor and somatosensory pathways also decrease initially but then from the age of 5 years progressively increase in proportion to arm length. 6. The threshold stimulus intensity for evoking muscle responses following electromagnetic stimulation of the cortex is high initially and falls progressively until the age of 16 years. A linear relationship exists between the threshold intensity and height for the height range 70-180 cm. 7. The threshold stimulus intensities for exciting peripheral motor and somatosensory nerves decrease up to the age of 5 years and then reach a plateau. 8. The results support the conclusion, already reported in the literature that peripheral nerves attain maximum value for fibre diameter and conduction velocity at approximately 5 years of age. 9. In contrast, it is concluded that the maximum fibre diameters in both motor and somatosensory central pathways increase in proportion to height, leading to constant central conduction delays with growth.

Adolescent↗
PubMed1991

Persistent reaction in paucibacillary leprosy: case reports.

Three patients of histopathologically confirmed borderline-tuberculoid leprosy showing no acid-fast bacilli and with lesions confined to the face, 2 on the cheek and 1 on the forehead, were given multidrug therapy as recommended by the WHO for paucibacillary cases. Within 3 months the lesions showed signs of upgrading (or reversal) reaction which was substantiated by histopathology. In 1 patient the facial nerve was affected leading to facial palsy. The lymphocyte transformation test did not show a significant rise. All 3 patients were given oral prednisolone for periods varying between 5 and 7 months, but the response was poor except in 1 patient in whom the facial palsy responded favourably. Injections of sodium antimony gluconate tried in 1 patient after stoppage of steroids did not control the reaction. After 18 months of regular follow-up during therapy, the cutaneous reaction in the patient with facial nerve involvement subsided leaving significant atrophy. However, in the other 2 patients the skin lesion persisted with clinical and histopathological evidence of upgrading reaction. The reasons for the unnatural persistence of reaction in these patients is not clear.

Adolescent↗
PubMed1991

Post-kala-azar dermal leishmaniasis: a case report strikingly resembling lepromatous leprosy.

An adult man with post-kala-azar dermal leishmaniasis who had lessons distributed in a manner strikingly similar to lepromatous leprosy is described. He was mistakenly treated with multidrug therapy as recommended by the WHO Expert Committee on leprosy. All investigations including slit-skin smears, histopathology, culture for Leishmania donovani and an indirect fluorescent antibody test to confirm post-kala-azar dermal leishmaniasis proved futile. The diagnosis was ultimately based on the previous history of kala-azar, the absence of other disorders which were ruled out by relevant laboratory tests and the good therapeutic response to sodium antimony gluconate. The epidemiological significance of this case and the salient points to distinguish this condition from leprosy are discussed.

Animals↗
PubMed1991

Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency.

Gyrate atrophy (GA) is an autosomal recessive eye disease characterized by progressive loss of vision due to chorioretinal degeneration. It is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase (OATase) with consequent hyperornithinemia. Although the clinical phenotype is largely confined to the eye, OATase deficiency is a systemic disorder. A step toward delineation of the enzyme defect in GA at the molecular level has been made by cloning and characterizing the cDNA and structural gene for OATase. The structural gene for OATase maps to chromosome 10 (10q26) and OATase-related sequences map to the X chromosome (Xp11.2). A diverse number of mutations at the OATase locus in GA patients of varied ethnic origins have been defined employing polymerase chain reaction and other molecular biological techniques. The majority of these mutations are of the missense type although a splicing mutation in one patient has recently been identified. The functional consequences of some of these mutations have been tested and confirmed in a eukaryotic expression system. These mutations demonstrate the allelic heterogeneity, which extends to both pyridoxine responsive and non-responsive forms of GA, reflecting the clinical and biochemical heterogeneity observed in this disease. The molecular studies in addition to providing information on the structure/function of the enzyme will facilitate understanding of the retinal pathophysiology in this disorder.

Base Sequence↗
PubMed1991

Multibacillary leprosy presenting as a solitary skin lesion; report of three cases and its significance in control programs.

Three patients with solitary skin lesions showing the cardinal signs of leprosy were seen and clinically classified among the paucibacillary cases. Initially, they were treated with two drugs (rifampin and dapsone) as recommended by the WHO Expert Committee. On the first visit of their follow-up, they were seen to be histopathologically either in the borderline (BB) or borderline lepromatous (BL) group, and acid-fast bacilli were demonstrated in the sections. Later they were put on three drugs (rifampin, dapsone and clofazimine) as given for multibacillary cases, and therapeutically they also behaved like bacilliferous leprosy. Such cases are rare and the reasons for the occurrence are not clear. Further studies on the subtle relationship between the local host factors and the virulence of the organisms grown from these lesions may offer an explanation. In light of these cases and previous reports of even lepromatous leprosy presenting as a single skin lesion, field workers--including both medical and paramedical workers--should carefully perform and interpret slit-skin smears from clinically diagnosed paucibacillary cases so that such unusual presentations of the disease are treated appropriately and not missed.

Adolescent↗
PubMed1990

Detection of point mutations associated with genetic diseases by an exon scanning technique.

A major challenge in genetics is identifying the basis of human heritable disease. We describe an "exon scanning" technique which surveys exons in genomic DNA for sequence alterations. By hybridizing genomic DNA to RNA probes derived from cDNAs, we can use RNase A to survey entire coding regions, comprising exons spread across extensive regions of genomic DNA, for mutations associated with genetic disease. Exon scanning of the beta-globin locus in the DNA of patients with 12 different hemoglobinopathies detected all of the culpable single base substitutions and deletions, but not single base insertions. Our analysis also revealed unsuspected polymorphisms and corrected a diagnosis originally based on hemoglobin electrophoresis. Exon scanning of the ornithine aminotransferase gene in a gyrate atrophy patient detected and localized a mutation in the sixth exon. Subsequent PCR amplification and sequencing characterized this as a missense mutation (proline----glutamine). Exon scanning of genomic DNA for sequence alterations, in combination with PCR amplification and sequencing, should be a generally useful strategy for evaluating suspect genes in disorders of unknown etiology, as well as for clinical diagnosis.

Base Sequence↗
PubMed1990

Giant nerve abscesses in leprosy.

Two leprosy patients with neuritis caused by giant abscesses involving almost the entire ulnar nerve are described. One patient, who also had skin lesions, was diagnosed histopathologically as having borderline tuberculoid leprosy both on skin and nerve biopsy, and the other, with only nerve involvement, belonged to the pure neuritic group. The lepromin test was strongly positive (with a vesicular reaction in one patient) and lymphocyte transformation to Mycobacterium leprae antigen was raised. These lesions can be easily mistaken for a peripheral nerve tumour in places where leprosy is uncommon. A brief account of the management of nerve abscess in leprosy is given.

Abscess↗
PubMed1990

Sporotrichosis in Nepal.

The first case of sporotrichosis from Nepal is reported in a 25-year-old man from a village about 60 km east of Kathmandu. He never travelled outside of Nepal before and had acquired the lymphocutaneous form of the disease after an accidental injury to the right foot while cutting wood. The diagnosis of the case was made by culturing Sporothrix schenckii from the lesions, proving the dimorphic character of the fungus in vitro, its pathogenicity in mice, and its serology. Oral potassium iodide therapy resulted in complete cure.

Adult↗
PubMed1990

Nodularity of nerves in treated leprosy.

Ten patients with fully treated paucibacillary leprosy, mainly tuberculoid, had asymptomatic nodules present along the peripheral nerves that persisted even after the skin lesions had completely subsided and treatment was stopped. Histopathology of the nodules revealed no signs of activity of the disease. The evolution, follow-up care, and significance of these nodules are discussed.

Adolescent↗
PubMed1990

Neurophysiological observations on corticospinal projections to the upper limb in subjects with Rett syndrome.

The aim of the present study was to investigate the excitability of corticospinal neurons and the integrity of their projections to the alpha motor neurons through the corticospinal tract in subjects of different ages with Rett syndrome. Electromagnetic stimulation of the motor cortex and cervical motor roots was used to evoke motor action potentials in the biceps brachii and hypothenar muscles. The phasic stretch reflex in the biceps brachii was also recorded to study the excitability of spinal alpha motor neurons. Motor cortex stimulation evoked motor action potentials at low threshold and with abnormally short latencies and prolonged durations. In contrast cervical motor root stimulation resulted in responses of normal latency and duration. The phasic stretch reflex had a low threshold, short latency and prolonged duration. It is concluded that in Rett syndrome the corticospinal pathway is intact. The results suggest disordered synaptic control of the Betz cell of the motor cortex and/or the spinal alpha motor neuron, although the involvement of the latter might be a consequence of dysfunction in supraspinal descending motor pathways.

Adolescent↗