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Biomedical subjects

J M Smith

Publications and source records attributed to J M Smith.

At least 253 records · Page 14Linked to original sources

The oral health status, dental needs and factors affecting utilisation of dental services in Asians aged 55 years and over, resident in Southampton.

A socio-dental investigation was carried out in Southampton among 195 Asians of Indian, Pakistani or Bangladeshi origin, aged 55 years and over, in order to assess their oral health status and identify factors which might affect their uptake of dental services. The majority of subjects (70%) were dentate; 69% were in need of periodontal treatment and 29% required extractions due to advanced periodontal involvement. Despite the fact that many subjects held positive attitudes towards dental health, less than 15% attended the dentist on a regular basis. The remaining subjects felt that it was not necessary to do so unless they were in pain or required new dentures.

Aged↗

Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts.

Ferritin is important in iron homeostasis. Its twenty-four chains of two types, H and L, assemble as a hollow shell providing an iron-storage cavity. Ferritin molecules in cells containing high levels of iron tend to be rich in L chains, and may have a long-term storage function, whereas H-rich ferritins are more active in iron metabolism. The molecular basis for the greater activity of H-rich ferritins has until now been obscure, largely because the structure of H-chain ferritin has remained unknown owing to the difficulties in obtaining crystals ordered enough for X-ray crystallographic analysis. Here we report the three-dimensional structure of a human ferritin H-chain homopolymer. By genetically engineering a change in the sequence of the intermolecular contact region, we obtained crystals isomorphous with the homologous rat L ferritin and of high enough quality for X-ray diffraction analysis. The X-ray structure of human H ferritin shows a novel metal site embedded within each of its four-helix bundles and we suggest that ferroxidase activity associated with this site accounts for its rapid uptake of iron.

Amino Acid Sequence↗

Isolation and sequence of a cDNA encoding mouse IMP dehydrogenase.

Inosinic acid (IMP) dehydrogenase (IMPD) catalyzes the conversion of IMP to XMP as the first committed step in GMP biosynthesis de novo. We have isolated a cDNA containing the complete coding region of mouse IMPD by its ability to complement a bacterial mutant lacking IMPD activity. Two independent cDNA clones were isolated by complementation, of which the longest was 1.7 kb in length. Northern analyses, using the IMPD cDNA as a probe, indicated that mature IMPD mRNA was a single species approx. 2.0 kb in size. Mouse IMPD is almost identical to Chinese hamster and human IMPDs and is highly conserved between Escherichia coli and mouse, with a direct amino acid (aa) identity of 39%, which increases to 60% if conserved aa are considered. The leader region of our longest cDNA clone is G + C-rich and contains two tandem copies of a G + C-rich direct repeat.

Amino Acid Sequence↗

Localized sex in bacteria.

Electrophoretic studies suggest that bacterial populations consist of a number of independent clones and that genetic recombination is rare in nature. But DNA sequencing reveals that individual bacterial genes have a mosaic structure that could have arisen only by recombination. How can these observations be reconciled and what is their relevance to prokaryotic evolution?

Bacteria↗

Altered phospholipase activities related to alpha 1-adrenergic receptor supersensitivity of aortas from aldosterone-salt hypertensive rats.

Many of the concepts presented in this paper are summarized in Fig. 7. Some aspects are well supported while others are speculative. The operation of PLC in VSM is well established, and in some hypertensive models (AHR, SHRSP) PLC assays exhibited altered activation. Currently this pathway leading to the production of IP3 and DAG is considered to be the major regulator of Ca release from sarcoplasmic reticulum (SR) and Ca entry by channels (CaC). Regulation of PKC by [Ca]i and DAG is thought to play a major role in controlling Ca entry. PKC has also been proposed to regulate PLA2 as well as PLD in conjunction with elevated [Ca]i. An important issue to be resolved is whether receptor regulation of other lipases occurs independently of the PLC-[Ca]i-PKC axis. Currently information supporting receptor regulation is lacking for VSM, but few studies have been conducted. Our observation that NE stimulation of PLD activity occurs in VSM indicates that the control of VSM by biochemical messengers is much more complicated than previously proposed. This seemingly redundant pathway may allow VSM to use alternate substrates for producing PA and DAG than are readily available to PLC. It also allows PA to be produced directly without phosphorylation of DAG. Although the role of PA in the regulation of Ca entry was proposed earlier, definitive studies establishing this linkage are still required. Any PLD activity on PIP2 would produce biochemical messengers (PA, DAG) which could stimulate Ca entry without producing the messenger, IP3, associated with Ca release (inactive IP2 would be produced). If PLC and PLD were independently regulated by receptor-guanine nucleotide-regulatory protein (G-protein) complexes, this would offer the potential for some agonists to excite VSM by Ca release and Ca entry mechanisms while others may excite by Ca entry alone. This system would also circumvent the problem of limited substrate for cellular regulation of [Ca]i if PIP2 were the primary substrate. This limitation does not exist with other phospholipids such as phosphatidylcholine which is a preferred substrate for PLD. The presence of multiple phospholipases under separate receptor regulation allows for a wider range of tissue responses to various agonists, than a system which is linked only through the PLC-[Ca]i-PKC axis. The presence of a PLD pathway also reopens the interpretation of previous studies which demonstrated a resetting between receptor occupancy and production of second messengers by PLC.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗

The location of exon boundaries in the multimeric iron-storage protein ferritin.

The nature of the amino acids whose codons border introns in ferritin genes is novel; the disposition of these intron boundaries within the three-dimensional structure of the 24-subunit molecule differs significantly from that of other proteins. These observations are discussed in relation to the functions of isoferritins.

Amino Acid Sequence↗

The cost of an intensive care unit: a prospective study.

The cost of intensive care for patients admitted to the ICU were estimated. Patients suffering from severe combined acute respiratory and renal failure who required mechanical ventilation and renal replacement therapy (SCARRF-D) cost per day significantly more than non-renal patients (pounds 938 compared to pounds 653 per patient respectively) and their average length of stay in hospital is nearly 4 times as long (28.8 compared to 7.6 days respectively). Approximately 44% of the total cost was staff related (28% for the provision of nurses and 16% for the rest). Retrieving information related to cost was difficult, time consuming and labour intensive.

Adult↗

Oltipraz-induced decrease in the activity of cytosolic glutathione S-transferase in Schistosoma mansoni.

The activity of glutathione S-transferase (GST) decreased progressively in Schistosoma mansoni from mice treated with oltipraz (OPZ). However, the peroxidase activity of GST (selenium-independent) and selenium-dependent glutathione peroxidase was not affected by OPZ treatment. Purification and quantification of GST from worms after OPZ treatment indicated that the decrease in enzyme activity was greater than could be accounted for by the decrease in GST protein content. SDS-polyacrylamide gel electrophoresis followed by Western blot analysis with GST isoenzyme specific antisera revealed a slight decrease in the quantity of both 26 and 28 kDa GSTs. Fractionation of cytosolic GSTs from male S. mansoni by chromatofocusing resolved three major isoenzymes (SmI, II and III) and a minor form which eluted first from the column. SmI, II and III all had a molecular weight of about 28 kDa on SDS-polyacrylamide gel electrophoresis. However, on electrophoresis in the absence of SDS, the three GST forms exhibited different mobilities. The pattern of SmI, II and III was similar in untreated and OPZ-treated worms, but the activities of the isoenzymes from treated worms were lower. The results suggest that OPZ interacts with the GST isoenzymes SmI, II and III in a similar manner; thus, the effects are not isoenzyme specific. Taken together, these results suggest that OPZ and/or its metabolites interact directly with GST resulting in inhibition of activity and reduction in total enzyme protein. This mechanism may be important in the antischistosomal action of OPZ.

Animals↗

A simple electrical-mechanical model of the heart applied to the study of electrical-mechanical alternans.

Recent evidence has shown that a subtle alternation in the surface ECG (electrical alternans) may be correlated with the susceptibility to ventricular fibrillation. This paper presents evidence that a mechanical alternation in the heart beat (mechanical alternans) generally accompanies electrical alternans. A simple finite-element computer model, which emulates both the electrical and mechanical activity of the heart, is presented. A pilot animal study is also reported. The computer model and the animal study both found that 1) there exists a regime of combined electrical-mechanical alternans during the transition from a normal rhythm towards a fibrillatory rhythm, 2) the detected degree of alternation is correlated with the relative instability of the rhythm, and 3) the electrical and mechanical alternans may result from a dispersion in local electrical properties leading to a spatial-temporal alternation in the electrical conduction process.

Animals↗

Geographical differences in adverse drug reaction reporting rates in the Northern Region.

The reporting rates of adverse drug reactions in the Northern Region have been examined with respect to source (hospital or general practice) and district of origin for the 3 years 1986-88. Mean annual reporting rates, corrected for population, or clinical activity, varied approximately 4-fold in general practice (0.066 to 0.257 reports per 1000 resident population) and more than 12-fold in hospitals (0.14 to 1.77 reports per 1000 deaths and discharges). There was no correlation between hospital and general practice reporting rates in the same health district. Overall more reports were received from general practice (1606) than hospitals (1000), although proportionally more reports of serious adverse reactions originated from hospitals. The reasons for these differences are unclear.

Drug-Related Side Effects and Adverse Reactions↗

Extramammary Paget's disease and prostatic carcinoma.

A patient with perianal extramammary Paget's disease (EMPD) occurring simultaneously with prostatic adenocarcinoma is presented. Four previously reported cases of genital EMPD associated with prostatic carcinoma are reviewed. The use of immunohistologic techniques to help establish the diagnosis in some cases, and the relationship of EMPD to underlying adenocarcinoma of sweat glands and of the lower urinary and gastrointestinal tracts is discussed. The importance of a directed search for internal malignancy in the individual patient with EMPD is emphasised.

Adenocarcinoma↗

Complex regulation of TGF beta expression by retinoic acid in the vitamin A-deficient rat.

We report the results of a histochemical study, using polyclonal antipeptide antibodies to the different TGF beta isoforms, which demonstrates that retinoic acid regulates the expression of TGF beta 2 in the vitamin A-deficient rat. Basal expression of TGF beta 2 diminished under conditions of vitamin A deficiency. Treatment with retinoic acid caused a rapid and transient induction of TGF beta 2 and TGF beta 3 in the epidermis, tracheobronchial and alveolar epithelium, and intestinal mucosa. Induction of TGF beta 1 expression was also observed in the epidermis. In contrast to these epithelia, expression of the three TGF beta isoforms increased in vaginal epithelium during vitamin A deficiency, and decreased following systemic administration of retinoic acid. Our results show for the first time the widespread regulation of TGF beta expression by retinoic acid in vivo, and suggest a possible mechanism by which retinoics regulate the functions of both normal and pre-neoplastic epithelia.

Animals↗