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Biomedical subjects

J M Smith

Publications and source records attributed to J M Smith.

At least 199 records · Page 11Linked to original sources
PubMed1994

Asthma and atopy as diseases of unknown cause. A viral hypothesis possibly explaining the epidemiologic association of the atopic diseases and various forms of asthma.

The basic etiology of asthma and atopy is unknown. Family grouping of cases is evident and has led to the assumption that genetic predisposition to making excessive IgE responses and in some cases a genetically determined tendency to have irritable bronchi are the fundamental causes of these conditions. Interplay between these hereditary predispositions and environmental factors such as allergen exposure are thought to explain all of the characteristic findings. Many cases, however, develop without a positive family history, and there are a variety of findings not easily explained by current theory. The increasing incidence of these conditions makes it necessary to question long held assumptions and explore other hypotheses. A review of difficult to explain characteristics and epidemiology of asthma and atopy makes a hypothesis involving a transmissible agent or agents plausible enough to warrant serious consideration.

Asthma↗
PubMed1994

Subclavian steal syndrome. A review of 59 consecutive cases.

Subclavian steal syndrome results from reversal of flow through the vertebral artery from occlusion or stenosis of the proximal subclavian or brachiocephalic artery. The resulting "steal" phenomenon leads to the common symptoms of vertigo, syncope, and intermittent claudication of the involved upper extremity. However, these symptoms rarely, if ever, result in permanent neurological damage in and of themselves. A significant percentage of patients will have concomitant extracranial atherosclerotic disease present. Visual disturbances and transient paralysis occur more often in patients with coexistent carotid disease. Carotid artery endarterectomy should be performed first in these patients and will likely resolve all symptoms. Carotid subclavian by-pass using a PTFE graft conduit remains the procedure of choice for patients suffering from disabling symptoms and can be performed with low operative risk and morbidity with excellent long term results.

Adult↗
PubMed1994

Schistosoma mansoni eggs as a target for praziquantel: efficacy of oral application in mice.

A study was undertaken to investigate the effect of administering a double oral dose of praziquantel (PZQ), given 9 days apart, on the egg viability in Schistosoma mansoni infected mice. The viability of eggs trapped in the tissues and those excreted in the faeces was determined using morphological (oogram) and function (egg hatching) criteria. Nine days after the first dose of PZQ, 90.5% of eggs excreted in the faeces were judged to be viable by the egg hatch method, as were 98.0% of eggs excreted from the control mice. However, only 44.0% of the eggs isolated from the intestine of PZQ treated mice were viable compared with 82.5% in the pretreatment group or 93.0% in the control group. Similar results were obtained for viability of eggs isolated from the intestine, by both the hatching and oogram methods. There was a dramatic reduction in the viability of eggs in liver tissue 9 days after the first dose of PZQ (13.0%) when compared with either the untreated controls (85.3%) or eggs in the livers of mice prior to PZQ treatment (80.0%). Following a second dose of PZQ (69 DPI), no eggs were detected in the faeces by 78 DPI, and eggs in the tissues were no longer viable. These data confirm the susceptibility of mature eggs of S. mansoni to a single dose of PZQ, but also demonstrate that the remaining immature eggs are undamaged and mature in the tissues of infected mice. Administration of a second dose of PZQ, 9 days after the first is suggested as an alternative treatment strategy assuring killing of all the schistosome eggs.

Administration, Oral↗
PubMed1993

The origin of chromosomes. I. Selection for linkage.

A model is analysed of cells containing independently replicating genes, which segregate randomly when the cell divides. We follow the fate of a primitive chromosome, in which two genes are linked, so that they replicate and segregate together. Such a chromosome increases in frequency in the population provided that (i) the two genes act synergistically, so that a cell containing at least one copy of each grows faster than a cell lacking one or other, and (ii) the number of genes per cell is small. The increase in frequency occurs even if the chromosome takes twice as long as an individual gene to replicate, giving a two-fold selective disadvantage within a cell. The increase occurs because a gene that is linked does not run the risk of finding itself, in the next generation, in a cell that lacks its synergistic partner.

Animals↗
PubMed1993

The evolution of chromosomes. II. Molecular mechanisms.

It is likely that there was a phase in evolution when the genome consisted of unlinked RNA genes, separately replicated. In this paper, we suggest molecular mechanisms whereby (i) separate RNA genes could have become linked to form chromosomes, (ii) monocistronic transcripts could have been made from these chromosomes, and (iii) RNA was replaced by DNA as the genetic material.

Animals↗
PubMed1993

Haem and non-haem iron sites in Escherichia coli bacterioferritin: spectroscopic and model building studies.

The bacterioferritin (BFR) of Escherichia coli is an iron-storage protein containing 24 identical subunits and between three and 11 protohaem IX groups per molecule. Titration with additional haem gave a maximum loading of 12-14 haems per molecule. The e.p.r. spectra and magnetic c.d. spectra of the protein-bound haem show it to be low-spin Fe(III), and coordinated by two methionine residues as previously reported for BFRs isolated from Pseudomonas aeruginosa and Azotobacter vinelandii [Cheesman, Thomson, Greenwood, Moore and Kadir, Nature (London) (1990) 346, 771-773]. A recent sequence alignment indicated that BFR may be structurally related to ferritin. The molecular model proposed for E. coli BFR has a four-alpha-helix-bundle subunit conformation and a quaternary structure similar to those of mammalian ferritins. In this model there are two types of hydrophobic pocket within which two methionine residues are correctly disposed to bind haem. The e.p.r. spectra also reveal a monomeric non-haem Fe(III) species with spin, S = 5/2. On the basis of sequence comparisons, a ferroxidase centre has recently been proposed to be present in BFR [Andrews, Smith, Yewdall, Guest and Harrison (1991) FEBS Lett. 293, 164-168] and the possibility that this Fe(III) ion may reside at or near the ferroxidase centre is discussed.

Amino Acid Sequence↗
PubMed1993

How clonal are bacteria?

Data from multilocus enzyme electrophoresis of bacterial populations were analyzed using a statistical test designed to detect associations between genes at different loci. Some species (e.g., Salmonella) were found to be clonal at all levels of analysis. At the other extreme, Neisseria gonorrhoeae is panmictic, with random association between loci. Two intermediate types of population structure were also found. Neisseria meningitidis displays what we have called an "epidemic" structure. There is significant association between loci, but this arises only because of the recent, explosive, increase in particular electrophoretic types; when this effect is eliminated the population is found to be effectively panmictic. In contrast, linkage disequilibrium in a population of Rhizobium meliloti exists because the sample consisted of two genetically isolated divisions, often fixed for different alleles: within each division association between loci was almost random. The method of analysis is appropriate whenever there is doubt about the extent of genetic recombination between members of a population. To illustrate this we analyzed data on protozoan parasites and again found panmictic, epidemic, and clonal population structures.

Animals↗
PubMed1993

Overproduction, purification and characterization of the bacterioferritin of Escherichia coli and a C-terminally extended variant.

The bacterioferritin (BFR) of Escherichia coli is an iron-sequestering haemoprotein composed of 24 identical polypeptide chains forming an approximately spherical protein shell with a central iron-storage cavity. BFR and BFR-lambda, a variant with a 14-residue C-terminal extension, have been amplified (120-fold and 50-fold, respectively), purified by a new procedure and characterized. The overproduced BFR exhibited properties similar to those of natural BFR, but the iron content (25-75 non-haem Fe atoms/molecule) was 13-39-fold lower. Two major assembly states of BFR were detected, a 24-subunit protein (tetracosamer) and a novel haem-containing subunit dimer. BFR-lambda subunits assembled into tetracosamers having the same external-surface properties as BFR, presumably because their C-terminal extensions project into and occupy about 60% of the central cavity. As a result, BFR-lambda failed totake up iron under conditions that allowed incorporation into BFR in vitro. The haem content of BFR-lambda (1-2 haems/tetracosamer) was lower than that of BFR (3.5-10.5 haems/tetracosamer) and this, together with a difference in the visible spectra of the two haemoproteins, suggested that the C-terminal extensions in BFR-lambda perturb the haem-binding pockets. A subunit dimer form of BFR-lambda was not detected. A combination of Mössbauer spectroscopy and electron diffraction showed that the BFR loaded with iron in vitro has a ferrihydrite-like iron core, whereas the in-vivo loaded protein has an amorphous core.

Amino Acid Sequence↗
PubMed1993

Expression of sulfated glycoprotein 2 is associated with carcinogenesis induced by N-nitroso-N-methylurea in rat prostate and seminal vesicle.

To understand the molecular mechanism of carcinogenesis in androgen-dependent tumors, we have searched for new markers which are associated with this process. In normal rat prostate and seminal vesicle, sulfated glycoprotein 2 (SGP-2) messenger RNA is barely detectable. However, we have found high levels of SGP-2 expression in the epithelial component of carcinomas of the prostate and seminal vesicle after initiation with N-nitroso-N-methylurea and promotion with testosterone propionate. We have also observed induction of SGP-2 expression in epithelial cells at early stages in carcinogenesis when cytologically malignant cells first begin to appear. SGP-2 has been reported previously to be associated with a variety of models of programmed cell death (apoptosis), including the prostate following castration. Our present findings provide a novel marker for carcinogenesis in the rat prostate and seminal vesicle.

Animals↗
PubMed1993

In situ ESWL for ureteric calculi: the optimum treatment?

In situ ESWL for ureteric calculi is associated with good stone clearance rates but is it without significant morbidity? A review of 189 patients with single ureteric calculi (150 upper ureter, 39 lower ureter calculi) revealed an 89% stone clearance for upper ureteral calculi and 80% stone clearance for lower ureteral calculi. However 11% of patients with upper ureteral calculi and 20% of patients with lower ureteral calculi required additional intervention for complications or failed treatment. In situ ESWL may not be the optimum therapy for all ureteric calculi especially those in the lower ureter.

Adolescent↗
PubMed1993

Construction and pathogenicity of Aspergillus fumigatus mutants that do not produce the ribotoxin restrictocin.

Aspergillus fumigatus, the most common cause of invasive pulmonary aspergillosis (IPA), produces a potent cytotoxin called restrictocin. To investigate the role of restrictocin in IPA, we have constructed fungal strains in which the res gene has been inactivated by gene disruption. These disruptants lack the specific extracellular ribonucleolytic activity associated with restrictocin, as measured by an in vitro rabbit reticulocyte lysate assay. Western blot analysis of one disruptant, using an anti-restrictocin monoclonal antibody, confirmed that the toxin is not produced. The growth characteristics of the disruptants could not be distinguished from those of their parental isolates on a variety of culture media. The pathogenicity of two disruptants was assessed in a murine model of IPA. There were no significant differences in mortality when these strains were compared with the parental isolates and an ectopic transformant. In addition, histological examination of infected lung tissue did not reveal any obvious differences in the number or size of fungal colonies or in the polymorphonuclear leucocyte response. Our results demonstrate that restrictocin is not an important virulence factor in this model of IPA.

Allergens↗
PubMed1993

A new ultrasensitive chemiluminescent assay for the site-specific quantification of alkaline phosphatase in gingival crevicular fluid.

The search for markers of periodontal disease activity and progression has accelerated over the last decade, in an effort to replace existing subjective clinical measures of periodontal health status. Research is being aimed at establishing more objective and quantitative methodology, capable of rapid diagnosis prior to the appearance of clinical signs of destructive disease. Such tests need to be sensitive enough to evaluate individual periodontal sites in health as well as disease states. We report the development of a new chemiluminescent assay for the enzyme alkaline phosphatase, that is capable of quantifying the enzyme in sub-microliter volumes of gingival crevicular fluid and serum. The technique will measure alkaline phosphatase (ALP) whilst immobilised on paper strips, without the need for an elution stage. It is simple, versatile and amenable to chair-side use. We discuss in detail the assay procedure and have examined levels of ALP in 11 adult volunteers with clinically healthy periodontal tissues. The mean ALP concentration was 2135 IU/L for GCF and 183 IU/L for serum, a 12-fold difference. There also appeared to be an "oral pattern" of enzyme distribution in healthy periodontal sites, with levels being higher in the anterior region of the mouth and highest in the lower anterior region.

Adamantane↗
PubMed1993

Evidence for a novel glycinamide ribonucleotide transformylase in Escherichia coli.

We demonstrate here that Escherichia coli synthesizes two different glycinamide ribonucleotide (GAR) transformylases, both catalyzing the third step in the purine biosynthetic pathway. One is coded for by the previously described purN gene (GAR transformylase N), and a second, hitherto unknown, enzyme is encoded by the purT gene (GAR transformylase T). Mutants defective in the synthesis of the purN- and the purT-encoded enzymes were isolated. Only strains defective in both genes require an exogenous purine source for growth. Our results suggest that both enzymes may function to ensure normal purine biosynthesis. Determination of GAR transformylase T activity in vitro required formate as the C1 donor. Growth of purN mutants was inhibited by glycine. Under these conditions GAR accumulated. Addition of purine compounds or formate prevented growth inhibition. The regulation of the level of GAR transformylase T is controlled by the PurR protein and hypoxanthine.

Acyltransferases↗
PubMed1993

Effects of dietary fish oil on cardiovascular responsiveness to adrenergic agonists in spontaneously hypertensive rat.

To test the hypothesis that dietary fish oil supplementation decrease systolic blood pressure in hypertensive rats by modifying cardiovascular responsiveness to adrenergic agonists, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) received either a corn or fish oil diet, 5% (g/kg) for 10 weeks. Mean aortic pressure was lower in fish oil treated (161 +/- 7 mm Hg (1 mmHg = 133.3 Pa)) than corn oil treated (191 +/- 6 mmHg) SHR. Although dietary fish oil supplementation decreased responsiveness to norepinephrine in isolated thoracic aorta from SHR, there was no change in cardiovascular responsiveness to the beta 1 agonist dobutamine or the alpha 1 agonist phenylephrine when these adrenergic agonists were administered in vivo. However, dietary fish oil did decrease the spontaneous basal tone in aorta from both SHR and WKY. This study provides further evidence that dietary fish oil lowers blood pressure in an animal model genetically predisposed to hypertension. However, the mechanism for this decrease in mean aortic pressure in vivo does not appear to be related to modification of cardiovascular responsiveness to alpha 1- or beta 1-adrenergic agonists and may be related to a decrease in basal vasomotor tone.

Adrenergic alpha-Agonists↗
PubMed1993

Antiepileptic drugs for the treatment of panic disorder.

Evidence from preclinical studies, preliminary clinical reports, pharmacologic challenge studies and a small number of controlled trials suggests that several antiepileptic agents--valproate, carbamazepine, and clonazepam--may have therapeutic effects in the treatment of patients with panic disorder. We review the theoretical basis and available clinical data supporting the use of these agents in panic disorder.

Anticonvulsants↗