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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 199 records · Page 11Linked to original sources
PubMed1997

A multidistrict audit on the management of Chlamydia trachomatis in genitourinary medicine clinics in Yorkshire.

Nine genitourinary clinics (one teaching hospital and 8 district general hospitals) within the Yorkshire Deanery audited the management of uncomplicated genital chlamydial infections in male and female patients attending between January and December 1995. Standards set included: 100% of chlamydia-positive patients to be treated within 2 weeks of diagnosis; 100% of patients to return for test of cure within one month of treatment; 100% of patients to be referred for contact tracing. Four hundred and thirty-six of a total 1356 cases were audited. Eighty-nine per cent received treatment within 2 weeks; 64% returned for a test of cure within one month; 93% were referred for contact tracing. Changes in practice and a region-wide multidisciplinary audit initiative resulted from the study.

Chlamydia Infections↗
PubMed1997

Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading.

To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

Animals↗
PubMed1997

Epidemiology of choanal atresia with special reference to the CHARGE association.

OBJECTIVE: To present epidemiologic data on the relatively rare malformation choanal atresia, based on a large collection of material and with special stress on the significance of the so-called CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital anomaly, and ear defect with deafness) association. METHODS: Data from three large registries of congenital malformations were used. Based on more than 5 million births, 444 infants with choanal atresia were identified. RESULTS: The average rate of choanal atresia is 0.82 per 10,000 and varies among programs. There is no statistically significant difference between races in rates, even though white infants have a higher rate than those of other races. The higher rate found in the California program is mainly attributable to unilateral, isolated cases. Unilateral atresia occurs equally often on the right and left. Among all cases of choanal atresia, the sex distribution is normal, a slightly increased risk at twinning exists, and no effect of maternal age or parity is seen. Chromosome anomalies are found in 6% of infants with choanal atresia, and 21 infants (5%) have monogenic syndromes or conditions. An analysis of associated malformations (present in 47% of the infants without chromosome anomalies) indicated that although a weak nonrandom association can be demonstrated between the malformations entering the so-called CHARGE complex, only a small proportion of infants with choanal atresia and other components of that condition probably represent this entity. The term CHARGE association seems to be overused in clinical practice. CONCLUSION: To be meaningful, the term CHARGE should be restricted to infants with multiple malformations and choanal atresia and/or coloboma combined with other cardinal malformations (heart, ear, and genital) and with a total of at least three cardinal malformations. Growth retardation should not be used in the definition.

Abnormalities, Multiple↗
PubMed1997

Current Management of Patients with Ductal Carcinoma-in-Situ.

Because of the wider use of screening mammography, ductal carcinoma-in-situ, or DCIS, once rare, is now diagnosed with increasing frequency. Important questions remain unresolved regarding the natural history, classification, and management of DCIS. Many physicians have assumed that DCIS is diffuse and regularly progresses to invasive cancer; therefore, they routinely recommend mastectomy. However, as we learn more about this lesion, it is now clear that in many cases the lesion is focal in extent, "premalignant," and curable with local procedures short of mastectomy. In this review, we describe the current state of knowledge regarding the presentation, pathology, natural history, and management of DCIS.

Journal Article↗
PubMed1997

Studies of the 6.7 family of dispersed genomic fragments within the MHC class I Region.

Searches for MHC-encoded disease susceptibility genes have led to considerable knowledge of the content of the class I region. In an effort to further understand the nature of the five 6.7 family members previously mapped to this region of the genome, we have further analyzed the cross-reactive members of the family and have observed additional genomic instability within the HLA-A subregion. Such genomic variation may underscore the slower evolutionary rates of the HLA-A allelic family and the extended linkage disequilibrium of markers distal to this locus. Moreover, one of the largest genes associated with a member of the 6.7 family, the 3.8-1 gene found proximal to HLA-B, was found to demonstrate limited, composite similarity to RAG2 and complement C4a gene sequences. A pancreas-specific transcript embedded in a 6.7 cross-reactive fragment was found distal to HLA-H and suggests that the fragments have remained linked to transcriptionally active chromatin comprised of both a major class I gene and a second novel coding sequence since the time of their dispersal. The absence of a 6.7 fragment in the HLA-B subregions of higher nonhuman primates lends credence to the possibility that the great apes have suffered a recent deletion event within this region following the emergence of Homo sapiens.

Animals↗
PubMed1996

Functional expression of a recombinant unitary glutamate receptor from Xenopus, which contains N-methyl-D-aspartate (NMDA) and non-NMDA receptor subunits.

A cDNA encoding a 100-kDa subunit (XenNR1) of the N-methyl-D-aspartate (NMDA) glutamate receptor type has been cloned from Xenopus central nervous system. When XenNR1 is coexpressed in a mammalian cell line with a recently cloned 51-kDa non-NMDA receptor subunit (XenU1), also from Xenopus, it forms a functional unitary receptor exhibiting the pharmacological properties characteristic of both NMDA and non-NMDA receptors. Firstly, XenU1 can replace NR2 subunits, in complementing XenNR1 to introduce the ligand binding properties of a complete NMDA receptor. Second, responses to both NMDA and non-NMDA receptor agonists and antagonists were obtained in patch-clamp recordings from the cotransfected cells, but no significant responses were recorded when the cells were singly transfected. Third, from solubilized cell membranes from the cotransfected cells, an antibody to the NR1 subunit coprecipitated the binding sites of the non-NMDA receptor subunit. The unitary glutamate receptor has a unique set of properties that denote intersubunit interaction, including a glycine requirement for the responses to non-NMDA as well as to NMDA receptor agonists and voltage-dependent block by Mg2+ of the non-NMDA agonist responses.

Amino Acid Sequence↗
PubMed1996

A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting.

The voltage-gated sodium channel Scn8a is broadly distributed in brain and spinal cord. We have identified a missense mutation in Scn8a that is associated with cerebellar ataxia in the jolting mutant, a mild allele of the "motor endplate disease" locus. The jolting mutation results in substitution of Thr for an evolutionarily conserved Ala residue in the cytoplasmic S4-S5 linker of domain III. Introduction of the corresponding mutation into the rat brain IIA sodium channel shifted the voltage dependence of activation by 14 mV in the depolarizing direction, without affecting the kinetics of fast inactivation or recovery from inactivation. A shift in the threshold of the Scn8a channel could account for the reduced spontaneous activity of Purkinje cells, reduced inhibitory output from the cerebellum, and loss of motor control observed in jolting mice.

Amino Acid Sequence↗
PubMed1996

The effect of acute phase proteins on clearance of chromatin from the circulation of normal mice.

The clearance of nucleosome core particles and H1-stripped chromatin from the circulation of mice was examined. Radiolabeled chromatin preparations were injected into mice, and blood samples were obtained over 60 min. The animals were then killed, and the selected organs were collected and radioactivity was measured. The acute phase response (APR) was induced by i.p. injections of casein before some clearance studies. Serum amyloid P component, the major acute phase protein in mice, increased from 27 microg/ml to 339 microg/ml during the acute phase. The rate of chromatin clearance decreased during the acute phase in C57BL/10J mice. At 5 min, 18% +/- 3% of the originally measured radioactivity remained in control animals compared with 49% +/- 2% in acute phase animals (p < 0.001). Co-injection of either serum amyloid P component or C-reactive protein, the major acute phase protein in humans, caused a decrease in the rate of chromatin clearance similar to that observed following the induction of the APR. APR induction also caused a higher percentage of the chromatin to localize in the liver compared with the spleen, with the ratio changing from 10.2 +/- 0.7 to 16.1 +/- 1.9 (p < 0.004). In addition, the APR caused a decrease in the percentage of chromatin localized in the kidney. The lack of radioactivity associated with cells in the circulation indicates that complement is not a major factor in the clearance mechanism of chromatin. These findings suggest that the APR produces major changes in the rate and path of chromatin clearance. These changes may protect against deposition of chromatin in target organs of systemic lupus erythematosus.

Acute-Phase Proteins↗
PubMed1996

Changes in calcium responsiveness and handling during keratinocyte differentiation. Potential role of the calcium receptor.

Extracellular calcium concentrations (Cao) > 0.1 mM are required for the differentiation of normal human keratinocytes in culture. Increments in Cao result in acute and sustained increases in the intracellular calcium level (Cai), postulated to involve both a release of calcium from intracellular stores and a subsequent increase in calcium influx through nonspecific cation channels. The sustained rise in Cai appears to be necessary for keratinocyte differentiation. To understand the mechanism by which keratinocytes respond to Cao, we measured the acute effects of Cao on Cai and calcium influx in keratinocytes at various stages of differentiation. We then demonstrated the existence of the calcium receptor (CaR) in keratinocytes and determined the effect of calcium-induced differentiation on its mRNA levels. Finally, we examined the role of Cai in regulating both the initial rise in Cai after the switch to higher Cao and the activity of the nonspecific cation channel through which calcium influx occurs. Our data indicate that the acute Cai response to Cao is lost as the cells differentiate and increase their basal Cai. These data correlated with the decrease in CaR mRNA levels in cells grown in low calcium. However, calcium influx as measured by 45Ca uptake increased with differentiation in 1.2mM calcium, consistent with the increase in CaR mRNA in these cells as well as the calcium-induced opening of the nonspecific cation channels. We conclude that the keratinocyte contains a CaR that regulates both the initial release of Cai from intracellular stores and the subsequent increase in calcium flux through nonspecific calcium channels. A rising level of Cai may turn off the release of calcium from intracellular stores while potentiating the influx through the nonspecific cation channels. Differentiation of keratinocytes appears to increase the CaR, which may facilitate the maintenance of the high Cai required for differentiation.

Animals↗
PubMed1996

Dose-response study of dehydroepiandrosterone sulfate on dentate gyrus long-term potentiation.

Neurosteroids are produced peripherally by endocrine glands, as well as enzymatically in the glia from steroid hormone substrates. GABA receptor sites and Ca2+ channel currents are prime targets for neurosteroid actions, and their effects are concentration dependent. For this reason, and the fact that treatment with one of them, sulfated dehydroepiandrosterone (DHEAS), improves performance in tasks involving memory in aged rats, we explored the effect of this hormone on dentate gyrus long term potentiation (LTP) in a dose-response mode. Intact anesthetized rats (urethane, 1.5 g/kg) were used. Electrodes were stereotaxically positioned in the perforant path and dentate gyrus for stimulation (bifocal) and recording (monofocal). DHEAS (10, 20, and 30 mg/kg, dissolved in Nutralipid 10%) was injected into the femoral vein. Ten animals were used to study the effects of each dose, one injection per animal. Twenty control animals were randomly interspersed within the experimental groups and were injected solely with Nutralipid. The results showed a significant increase in LTP at all doses in relation to baseline values. Further, there were significant increments in amplitude at 20 and 30 mg in relation to 10 mg. However, the data did not reveal significant differences between the 20- and the 30-mg-treated rats. Results are discussed in terms of effects of DHEAS on neurotransmitter and Ca2+ channel ion systems.

Animals↗
PubMed1996

Contrast transfer characteristics of visual short-term memory.

A two interval forced choice constant stimuli method was used to determine: (i) the point of subjective equality (PSE); and (ii) the just-noticeable-difference (JND) in contrast for two luminance gratings, one held in short-term visual memory. Psychometric functions for delayed contrast discrimination were determined as a function of spatial frequency from 1 to 8 c/deg, reference contrast from 5 to 60% and inter-stimulus interval from 1 to 10 sec. The PSE for remembered contrast was invariant with spatial frequency and inter-stimulus interval for the three reference contrast levels tested. The JND contrast plotted against spatial frequency followed a U-shaped function with lowest thresholds at around 4 c/deg. The threshold function translates parallel to the sensitivity axis with an increase in either the reference contrast or the inter-stimulus interval. However, the bandpass shape of the threshold function is invariant with both reference contrast and inter-stimulus interval. At 1, 3 and 10 sec inter-stimulus intervals, contrast JNDs increase with reference contrast according to a power law with an average exponent of 0.70. Contrast JNDs also increase as a power function of the inter-stimulus interval with an average exponent of 0.38 for the three reference contrasts tested.

Contrast Sensitivity↗