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Biomedical subjects

K Ray

Publications and source records attributed to K Ray.

At least 109 records · Page 6Linked to original sources
PubMed1997

Undergraduate training in the European Union. Convergence or divergence?

A survey of dental schools in the European Union was carried out for two main reasons. Firstly to promote the exchange of information in respect of curriculum objectives in the different countries and secondly to ascertain the differences in the interpretation of the 1978 EU sectoral directives for dental education and training. Out of 127 schools, only 30 responded, yet the information provided is of considerable importance. It demonstrates wide divergence in the interpretation of the 1978 Directives and methods of assessment of clinical competence. There is a considerable difference throughout Europe in hours devoted to the various subjects included in the Dental Directives. There is little evidence of convergence in methods of assessment or quality assurance. The survey demonstrates the difference in resources, levels of staff, availability of clinical training places, output in research and patient treatments throughout the European Union. The results question the effectiveness of the 1978 Dental Directives in promoting convergence of standards. As there is free movement of dentists throughout the European Union, it is concluded that a different approach may be necessary to ensure that all European Union dental graduates achieve comparable standards in their education and training.

Curriculum↗
PubMed1997

Standardisation of polymerase chain reaction for the detection of Salmonella typhi in typhoid fever.

To improve the diagnosis of Salmonella typhi infection, a polymerase chain reaction (PCR) assay was developed for the amplification of the dH flagellin gene of S typhi. Primers were designed from dH flagellin gene sequence which will give an amplification product of 486 base pairs. In tests to study the specificity of the assay, no amplification was seen in non-salmonella strains or salmonella strains with flagellar gene other than "d". Sensitivity tests determined that 28 pg of S typhi target DNA or 3 x 10(2) target bacteria could be detected by the PCR assay. Subsequently, the PCR technique was used for detection of S typhi in blood or clot cultures from 84 patients clinically suspected of having typhoid fever, and from 20 healthy control subjects. Twenty five of 84 samples from clinically suspected cases were positive by PCR; four of which were culture negative. No amplification was seen in samples from patients who were culture positive for organisms other than S typhi or from controls. The time taken for each sample for PCR analysis was less than 48 hours compared with three to five days for blood or clot culture. PCR appeared to be a promising diagnostic test for typhoid fever.

DNA, Bacterial↗
PubMed1997

A Ca(2+)-sensing receptor mutation causes hypoparathyroidism by increasing receptor sensitivity to Ca2+ and maximal signal transduction.

Activating mutations of the Ca(2+)-sensing receptor (CaR) gene cause autosomal dominant hypoparathyroidism. Functional expression studies have been reported for several mutations, but have produced conflicting results. Thus, the mechanism by which these mutations activate the receptor is unclear. We describe here a new family with autosomal dominant hypoparathyroidism. The mother and three daughters experienced muscle spasms and/or seizures from early childhood. They were treated with oral calcium and vitamin D analogs, and all four patients developed hypercalciuria, nephrocalcinosis, and renal insufficiency. In this family, we identified a heterozygous missense mutation (F612S) involving the extracellular region of the CaR. The mutation cosegregated with disease. It was not present in 50 normal control individuals. We used site-directed mutagenesis to introduce this mutation into the CaR cDNA, and then expressed the mutant receptor in human embryonic kidney (HEK)-293 cells. In these cells, the accumulation of inositol phosphates was measured as a function of extracellular Ca2+ concentration. Compared with the wild-type receptor, the mutant receptor showed a left-shift in the concentration-response curve and an increase in the maximal response to high Ca2+ concentration. These effects did not appear to be mediated by changes in levels of receptor expression, as judged by ELISA, or by changes in receptor glycosylation, as judged by Western analysis. We conclude that this CaR mutation causes hypoparathyroidism by a dual increase in receptor sensitivity to extracellular Ca2+ and maximal signal transduction capacity.

Adult↗
PubMed1997

Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor.

Activating mutations of the Ca(2+)-sensing receptor (CaR) gene have been identified in families with autosomal dominant hypoparathyroidism and in one patient with sporadic hypoparathyroidism. Here, we describe two additional patients with sporadic hypoparathyroidism. One patient presented with mild symptoms at age 18 yr; the other was severely symptomatic from infancy. A heterozygous missense mutation was identified in each patient. One mutation (L773R) involved the fifth transmembrane domain of the CaR, the other (N118K) affected the amino-terminal, extracellular domain. In both cases, the probands' parents lacked the mutation, indicating that the mutations arose de novo. In expression studies the mutations shifted the concentration-response curve to the left and increased maximal activity. We conclude that 1) sporadic hypoparathyroidism can be caused by de novo gain-of-function mutations of the CaR; 2) the phenotype can vary from mild to life-threatening hypocalcemia; 3) gain-of-function mutations can involve not only extracellular regions, as previously reported, but also transmembrane domains of the CaR; and 4) the mechanism of activation can involve both increased receptor sensitivity to Ca2+ and increased maximal signal transduction.

Adult↗
PubMed1997

Development of the Drosophila olfactory sense organs utilizes cell-cell interactions as well as lineage.

We have examined the mechanisms underlying the development of the olfactory sense organs on the third segment of the antenna of Drosophila. Our studies suggest that a novel developmental strategy is employed. Specification of the founder or precursor cell is not governed by the genes of the achaete-scute complex. Another basic helix-loop-helix encoding gene, atonal, is essential for determination of only a subset of the sensilla types--the sensilla coeloconica. Therefore, we predict the existence of additional proneural genes for the selection of sensilla trichoidea and sensilla basiconica. The choice of a founder cell from the presumed proneural domain is regulated by Notch activity. Soon after delamination of the founder cell, two to three additional neighboring cells also take on a sensory fate and these cells together form a presensillum cluster. The selection of neighbors does not occur when endocytosis is blocked using a temperature sensitive allele of shibire, thus suggesting that cell-cell communication is required for this step. The cells of the cluster divide once before terminal differentiation which is influenced by Notch activity. The final cell number within each sensillum is controlled by programmed cell death.

Animals↗
PubMed1997

Seroprevalence of cytomegalovirus antibodies in patients attending STD and antenatal clinics.

Sera from 368 patients attending sexually transmitted disease (STD) and antenatal clinics were screened for cytomegalovirus (CMV) specific IgG and IgM by indirect ELISA. IgG was detected in 94% of patients tested. CMV IgM seropositivity was found in 8.5% of normal pregnant females and in none of the normal asymptomatic males. CMV-IgM was detected in higher number of patients with STD than in those without STD. There was slightly higher association of CMV IgM antibodies mainly with syphilis in males and chlamydial endocervicitis in females.

Adult↗
PubMed1997

Sero surveillance of HIV infection in high risk groups and in suspected AIDS cases in a New Delhi hospital.

A total of 17,824 sera were screened for the presence of HIV 1 + 2 antibodies by Enzyme Immuno Assay (EIA) to determine (i) seroprevalence of HIV infection in hospital high risk groups (ii) time trend of HIV seroprevalence in STD clinic attendees (both STD patients and non STD patients), over a period of six years, (iii) relationship of the STD's with HIV seropositivity (iv) clinical profile and epidemiological characteristics of the AIDS cases. A progressive increase in the HIV seropositive STD patients showing a five fold rise over six years was seen. Most gave history of multipartner sex especially with female CSW's. The most common STD associated with HIV seropositivity was Syphilis followed by Chancroid and Gonorrhoea. All had HIV-1 infection. The AIDS cases (20) presented mainly with tuberculosis, both pulmonary and extrapulmonary. The mode of infection, both in the HIV seropositive and AIDS cases, was mainly heterosexual relationship followed by blood transfusion. In a few cases, infection was perinatally transmitted. In the limited number of HIV positive contacts studied, seven were confirmed as Western Blot positive. HIV infection, although a later introduction in Delhi compared to the coastal cities, has shown a clear increasing trend in the STD patients.

Adolescent↗
PubMed1996

Cloning and characterization of the cDNA and gene encoding the gamma-subunit of cGMP-phosphodiesterase in canine retinal rod photoreceptor cells.

Rod photoreceptor cyclic GMP-phosphodiesterase (cGMP-PDE) is one of the key enzymes of the visual phototransduction cascade in the vertebrate retina. The enzyme is composed of alpha- and beta-catalytic subunits and two identical inhibitory gamma-subunits. A defect in any of the subunits may potentially alter the activity of the enzyme, leading to aberration in the visual phototransduction. We have cloned and sequenced both the cDNA and gene for the canine gamma-subunit of cGMP-PDE (PDE gamma). The 952-bp cDNA has a coding region of 261 bp which is very similar to those of the PDE gamma cDNAs from human, mouse and bovine retinas. Among the 87 amino acids encoded by the transcribed region, differences in only three residues located within the first 17 amino acids were identified. The carboxyl terminus of PDE gamma, involved in interaction with the catalytic subunits of cGMP-PDE and the alpha-subunit of transducin, is conserved through evolution. The single polyadenylation signal (AATAAA) present in human and bovine PDE gamma cDNAs is replaced by AGTAAA in the canine sequence. The canine gene (2.8 kb) consists of four exons and is much smaller than the human gene (6 kb). The larger size of the human gene is primarily due to the presence of AluI repetitive elements in its first two introns.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Effect of anthracycline antitumor antibiotics (adriamycin and nogalamycin) and cycloheximide on the biosynthesis and processing of major UsnRNAs.

In the present study, anthracycline antitumor antibiotics (e.g. adriamycin and nogalamycin), the potent RNA synthesis inhibitors and cycloheximide, the protein synthesis inhibitor, have been used to understand the events of biosynthesis and processing of major UsnRNAs (U1-U6). The anthracyclines inhibit the UsnRNAs biosynthesis (in terms of labelling) differentially in a dose dependent manner. The inhibitory effect of adriamycin and nogalamycin reached plateau at a concentration of 2.5 micrograms/ 10(6) cells/ml and 0.1 microgram/10(6) cells/ml respectively and indicates that nogalamycin is more inhibitory than adriamycin. The inhibition of the UsnRNAs synthesis (in terms of labelling) became maximum within 30 min of incubation and remained unaltered even after 2 h. Thus, it shows that the anthracyclines preferentially inhibit the initiation of the UsnRNA genes' transcription as it has been seen in cases of other large RNAs' synthesis by some other laboratories. The higher inhibitory effect of the anthracyclines on the biosynthesis of U5 and U6 compared to other UsnRNAs indicates the presence of more binding sites on the U5 and U6 snRNA genes. In presence of the anthracyclines, there was high retention of cytoplasmic major pre-UsnRNAs/ UsnRNAs which indicates that the elongation of the UsnRNA synthesis is probably impaired along with initiation; because for the proper processing of the pre-UsnRNAs, formation of the correct secondary structure of that pre-UsnRNA is necessary. Cycloheximide showed some differential effect on the pol II transcribed UsnRNAs (U1-U5) biosynthesis (in terms of labelling) however it has no effect on the pol III transcribed U6 snRNA. It implies that in the pol II transcribed UsnRNAs, some transacting labile factors, either activator or inhibitor, are involved. Whereas, the processing of the UsnRNAs (either pol II or pol III transcribed) was affected more or less in a similar fashion in presence of cycloheximide, indicating the involvement of some transacting labile factors in this event.

Animals↗
PubMed1996

Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster.

We report the molecular and genetic characterization of the cytoplasmic dynein light-chain gene, ddlc1, from Drosophila melanogaster. ddlc1 encodes the first cytoplasmic dynein light chain identified, and its genetic analysis represents the first in vivo characterization of cytoplasmic dynein function in higher eucaryotes. The ddlc1 gene maps to 4E1-2 and encodes an 89-amino-acid polypeptide with a high similarity to the axonemal 8-kDa outer-arm dynein light chain from Chlamydomonas flagella. Developmental Northern (RNA) blot analysis and ovary and embryo RNA in situ hybridizations indicate that the ddlc1 gene is expressed ubiquitously. Anti-DDLC1 antibody analyses show that the DDLC1 protein is localized in the cytoplasm. P-element-induced partial-loss-of-function mutations cause pleiotropic morphogenetic defects in bristle and wing development, as well as in oogenesis, and hence result in female sterility. The morphological abnormalities found in the ovaries are always associated with a loss of cellular shape and structure, as visualized by a disorganization of the actin cytoskeleton. Total-loss-of-function mutations cause lethality. A large proportion of mutant animals degenerate during embryogenesis, and the dying cells show morphological changes characteristic of apoptosis, namely, cell and nuclear condensation and fragmentation, as well as DNA degradation. Cloning of the human homolog of the ddlc1 gene, hdlc1, demonstrates that the dynein light-chain 1 is highly conserved in flies and humans. Northern blot analysis and epitope tagging show that the hdlc1 gene is ubiquitously expressed and that the human dynein light chain 1 is localized in the cytoplasm. hdlc1 maps to 14q24.

Alleles↗