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Biomedical subjects

S Love

Publications and source records attributed to S Love.

At least 181 records · Page 10Linked to original sources
PubMed1992

PCR-mediated search for herpes simplex virus DNA in sections of brain from patients with multiple sclerosis and other neurological disorders.

Herpes simplex virus (HSV) has been shown to cause central nervous system demyelination in experimental animals and several studies have implicated HSV in the aetiology of multiple sclerosis (MS). We have used the polymerase chain reaction to look for DNA of both type 1 HSV (HSV-1) and type 2 HSV (HSV-2) in formalin-fixed paraffin-embedded brain tissues from patients with MS and other neurological diseases. Primers which amplify a fragment of the normal cellular gene c-myc were included in the reactions to assess the preservation of DNA in the tissue samples. 77 plaques of demyelination from 23 patients with MS were examined. HSV-1 DNA was amplified from only one plaque. This plaque involved the trigeminal root entry zone in the pons and it is suggested that the presence of viral DNA was related to the site examined rather than to the demyelination per se. HSV-2 DNA was amplified from none of the plaques. As expected, HSV-1 DNA was detected in the brains of 6 patients who died of HSV-1 encephalitis and HSV-2 DNA was amplified from the brain of a neonate with congenital HSV-2 infection. In sections of brain from 39 patients with a wide range of other neurological diseases HSV-1 DNA was detected in the pons of only 1 patient, who had AIDS associated with cytomegalovirus ventriculitis; subsequent investigation confirmed the presence of concomitant HSV-1 brain stem infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of sodium butyrate on the expression of sodium channels by neuronal cell lines derived from the rat CNS.

We have studied the effects of sodium butyrate on cell morphology and the expression of mRNAs encoding voltage-gated sodium channels in five neuronal cell lines, B35, B50, B65, B103 and B104, all derived from the rat CNS. The cells were grown in medium supplemented with 2.5 mM sodium-n-butyrate and examined daily by phase-contrast microscopy. Sodium butyrate caused slowing of cell division and the formation of longer and more highly branched cytoplasmic processes than were present in untreated cells. Expression of sodium channel mRNA was analysed by PCR with primers that allow the transcripts encoding the different types of sodium channel to be distinguished according to the lengths of the PCR products. The identity of the PCR products was confirmed by restriction enzyme digestion. Southern blotting and hybridization with internal radiolabelled probes. Prior to sodium butyrate treatment, expression of sodium channel mRNA was largely restricted to B50 and B104 cells: B50 cells showed expression of rat brain types I and II sodium channel and B104 cells expressed rat brain type III sodium channel. After treatment for 5 days with sodium butyrate, sodium channel mRNA was detected in all five cell lines. In addition to type I and type II sodium channel, B50 cells expressed rat brain type III sodium channel. These three types of sodium channel were also expressed by B35, B65 and B103 cells. Even after butyrate treatment, B104 cells expressed only type III sodium channel. The treatment also induced expression of rat skeletal muscle SkM1 sodium channel in B35 cells but only trace amounts in the other neuronal cell lines.

Animals↗
PubMed1992

The development of naturally acquired cyathostome infection in ponies.

Groups of animals of different ages and experience of previous parasite exposure were allowed to graze a single pasture for 5 weeks in autumn (7 October to 11 November). There was evidence that previous exposure modified cyathostome development, as acquired burdens in foals which had previously grazed were smaller and developed more slowly than those of helminth-naive animals of the same age. The burdens acquired by yearling and adult ponies were of a similar size to those of the previously grazed foals, but the incidence of arrested development was higher in the younger groups of foals and yearlings when compared with adults. Further evidence of an effect of age on cyathostome development was that the level of faecal egg output of the adult ponies was lower than in the groups of young animals.

Age Factors↗
PubMed1992

The polymerase chain reaction and its applications in neuropathology.

The polymerase chain reaction (PCR) provides a means of generating large numbers of copies of selected segments of DNA. Once amplified, the DNA can be characterized by determination of its size and sequence. For many applications, routinely-processed biopsy and autopsy material is an adequate substrate for the reaction. PCR can be used to amplify sequences of DNA that are uniquely characteristic of particular micro-organisms, allowing their rapid detection in samples of tissue or cerebrospinal fluid. The technique allows clones of cells with gene rearrangements or translocations to be detected with great sensitivity and is proving a useful way to monitor the effects of tumour therapy, particularly in patients with lymphomas and leukaemias. Further applications include the identification of gene deletions and mutations, and the assessment of cell lineage by amplification and analysis of highly polymorphic gene loci (DNA fingerprinting). Because the degree of amplification resulting from PCR is so great, even a single molecule of contaminating DNa may be detected and its significance misinterpreted. Great care, therefore, should be taken to prevent contamination of samples, particularly by the products of previous reactions, and every series of reactions should include appropriate controls.

Animals↗
PubMed1992

Comparison of modified Bielschowsky silver impregnation and anti-ubiquitin immunostaining of cortical and nigral Lewy bodies.

We have compared the sensitivity of a modified Bielschowsky silver impregnation with that of anti-ubiquitin immunostaining for the detection of Lewy bodies in five cases of diffuse Lewy body disease. In two of the cases there were neuritic plaques and neurofibrillary tangles within the neocortex in sufficient numbers to warrant an additional diagnosis of Alzheimer's disease. The modified Bielschowsky technique was as effective as anti-ubiquitin immunohistochemistry at demonstrating cortical Lewy bodies in 7 micron-thick paraffin sections. As might therefore be expected, silver impregnation of 20 micron-thick sections revealed significantly more cortical Lewy bodies than did the immunostaining of 7 micron-thick sections (P = 0.004). The silver impregnation had the further advantage of allowing much better visualization of the Alzheimer-type changes. In contrast to the cortical-type Lewy bodies, the dense-core type present in sections of midbrain were relatively poorly impregnated by the modified Bielschowsky method, possibly reflecting differences in the composition of the two types of inclusion.

Aged↗
PubMed1992

Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia.

The metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.

Animals↗
PubMed1992

Cardiovascular alterations in the hypothyroid rat.

We conducted the present studies in intact animals to assess alterations in integrated cardiovascular function due to hypothyroidism. Rats were surgically thyroidectomized or sham operated. Most obvious among the alterations detected under resting conditions was the bradycardia present in hypothyroid animals. Cardiac output was significantly reduced by slower heart rate; however, mean arterial blood pressure and left ventricular +dP/dt were maintained. Total peripheral resistance was increased in hypothyroid animals. Functional responsiveness to hemodynamic challenges unmasked additional characteristics. Thyroidectomized animals had normal stroke index-left ventricular end diastolic pressure relationships in response to rapid volume infusion. Peak left ventricular +dP/dt response to brief aortic occlusion was attenuated in thyroidectomized animals. Hypothyroid rats failed to augment left ventricular -dP/dt in response to isoproterenol challenge. Moreover, isoproterenol failed to reduce total peripheral resistance in the hypothyroid rat. Therefore, the hemodynamic responses observed in the intact, hypothyroid animal are consistent with the presence of (a) decreased cardiac contractile protein ATPase, (b) reduced calcium uptake by cardiac sarcoplasmic reticulum and (c) altered vascular adrenergic receptors. Many cellular and subcellular defects are compensated by integrative mechanisms operating under resting conditions, while other defects are unmasked only when examined in the intact, functional cardiovascular system undergoing hemodynamic challenge.

Animals↗
PubMed1992

Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.

Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.

Adolescent↗
PubMed1992

Short term therapy (STT) for acute myelogenous leukaemia (AML).

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.

Adolescent↗
PubMed1991

Results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy.

To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied. Surgery typically consisted of local excision without evaluation of the microscopic margins of resection. The median radiation dose to the tumor site was 6400 cGy. With a median follow-up time of 81 months, eight patients (21%) have experienced a recurrence in the breast. The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months. The 5-year and 8-year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively. Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast. No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small. The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment. Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.

Adult↗
PubMed1991

Tumor enzymes and prognosis in transitional cell carcinoma of the bladder: prediction of risk of progression in patients with superficial disease.

The activities of 6 enzymes of carbohydrate metabolism were estimated in superficial transitional cell carcinomas from 103 patients undergoing transurethral resection of the bladder for the first time. The patients were followed by quarterly endoscopic examinations for a maximum of 81 months (median 33 months). During followup 24 patients had progressive disease. The activities of phosphofructokinase and phosphohexose isomerase were significantly lower in tumors from patients whose disease had superficially invaded the lamina propria (stage pT1) than in others in whom it was confined to the bladder mucosa (stage pTa). Similarly the activities of the 2 enzymes were significantly higher in well differentiated (grade 1) than in moderately well differentiated (grade 2) carcinomas. Univariate analyses using the log rank test showed that neither pathological stage nor malignancy grade of the carcinoma was a significant factor in predicting the risk of progression. Of the 6 enzymes, below median activities of phosphofructokinase, lactate dehydrogenase and phosphohexose isomerase were associated with a significantly increased risk of progression in these patients. Multivariate analyses using Cox's proportional hazards model showed that the activity of lactic dehydrogenase in superficial transitional cell carcinoma is an independent prognostic factor in predicting the risk of progression. It is postulated that the measurements of the activities of the 3 enzymes in tumors from patients with superficial transitional cell carcinoma might help to select individual patients with a high risk of progression for adjuvant intravesical treatments.

Age Factors↗
PubMed1991

Hope, social support and self-esteem of patients with spinal cord injuries.

A descriptive study was conducted to determine if a relationship among the variables of hope, social support and self-esteem existed in persons with spinal cord injuries. A demographic data sheet and three instruments were used: Miller Hope Scale (MHS), Personal Resource Questionnaire Part II (PRQ) and Rosenberg Self-Esteem Scale (RSES). Of the 83 inpatients and outpatients who agreed to participate, 77 sets of questionnaires were usable. Ages of subjects ranged from 18-73 (mean 34.8) years and levels of injury ranged from C4-L3. The mean scores on the tools were: MHS-153.51 (40-200 possible range), PRQ-137.42 (25-175 possible range) and RSES-29.59 (10-40 possible range). There was a statistically significant relationship between hope and social support, hope and self-esteem and social support and self-esteem. By multiple regression analysis, the best predictors of hope in the subjects were self-esteem, social support and education.

Adult↗
PubMed1991

Immunochemical detection of sodium channel in human tissue and cell lines.

Mouse monoclonal antibodies have been raised to the C-terminal region of rat type II voltage-dependent sodium channel. One of these, designated 13A4-G4, recognizes a 260 Kd putative sodium channel protein in human fetal brain, heart and skeletal muscle, at 14-18 weeks of gestation. Faint immunoreactivity is also present in human fetal kidney but none has been detected in human fetal liver, lung or spleen. The antibody reacts in both western blots and immunocytochemical preparations with the human neuroblastoma cell lines SK-N-SH and SK-N-MC, the rhabdomyoblastoma cell line TE671, Y79 retinoblastoma cells and IPSB-18 astrocytoma cells. No 13A4-G4 immunoreactivity has been detected in several human cell lines derived from tissues that do not normally express sodium channels.

Animals↗
PubMed1991

Autopsy neuropathological findings in 'burnt out' herpes simplex encephalitis and use of the polymerase chain reaction to detect viral DNA.

We have conducted an autopsy study of the brains of three patients with 'burnt out' temporal and frontal lobe encephalitis, thought to be due to previous herpes simplex virus infection. The brains showed marked atrophy and yellow-brown discolouration predominantly involving the anterior part of both temporal lobes. Histology revealed destruction of grey and white matter, perivascular and leptomeningeal aggregates of lymphocytes and macrophages, and severe gliosis. Immunohistochemistry for herpesvirus antigens was negative but, by use of the polymerase chain reaction, a segment of the thymidine kinase gene of herpes simplex virus type 1 was detected in sections of temporal lobe from all three brains. These findings support the hypothesis that herpes simplex virus may persist within the central nervous system after acute herpes encephalitis, to cause latent or low-grade productive infection.

Adult↗
PubMed1991

The isolation, characterisation and quantification of the equine plasma lipoproteins.

Plasma lipoproteins were isolated from eight Thoroughbred horses and eight Shetland ponies on the basis of particle size by gel filtration chromatography and according to density using rate-zonal ultracentrifugation. Three major classes corresponding to very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) were identified and characterised by their lipid and apolipoprotein compositions. The particle size distributions of each class were determined by electron microscopy and non-denaturing polyacrylamide gradient gel electrophoresis. HDL was found to dominate the equine lipoprotein spectrum, accounting for 61 per cent of the total plasma lipoprotein mass (VLDL 24 per cent, LDL 15 per cent). The VLDL class was isolated as a single population of particles that were triglyceride rich and cholesterol, phospholipid and protein poor. Equine LDL was characteristically cholesterol rich and was found to be polydisperse comprising three subfractions that were discrete with respect to particle size and lipid composition. The HDL class was composed of homogeneous particles that were typically protein rich. Apolipoprotein (apo) B was the major protein of VLDL and LDL, and presented two components on polyacrylamide gel electrophoresis with molecular weights in the region of human apoB-100 and a third in VLDL similar to that of apoB-48. ApoA-I was the predominant protein in equine HDL. Although there were no breed differences in the physical or chemical properties of each lipoprotein class, the Shetland ponies had higher plasma triglyceride and VLDL concentrations than their Thoroughbred counterparts.

Animals↗
PubMed1991

Use of the polymerase chain reaction to detect herpes simplex virus DNA in paraffin sections of human brain at necropsy.

The feasibility of detecting herpesvirus DNA in paraffin sections of routinely fixed and processed human necropsy brains by use of the polymerase chain reaction (PCR) was assessed. A 110 bp segment of the thymidine kinase gene of herpes simplex virus type 1 (HSV1) could readily be amplified in sections from the brains of six patients with acute HSV1 encephalitis but not from those of six patients with other neurological diseases, including varicella-zoster encephalitis and herpes simplex virus type 2 encephalitis. Primers suitable for amplifying c-myc were included in the PCRs for assessment of DNA preservation. This was found to be adequate to allow amplification of c-myc DNA in sections from all of the brains studied. The PCR provides a simple and specific means of detecting HSV1 DNA in routinely processed necropsy material.

Adolescent↗