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Biomedical subjects

M Kemp

Publications and source records attributed to M Kemp.

At least 91 records · Page 5Linked to original sources
PubMed1994

Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages.

The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had self-healing cutaneous leishmaniasis. The T-cell clones expressed CD4, and the alpha chain of the T-cell antigen receptor. GP63 reactive T-cell clones activated by antigen or by immobilized anti-CD3 antibody released relative large amounts of interferon-gamma and no or little interleukin-4, thereby resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells recognizing gp63 can take part in the host defence against L. major infections.

Adult↗
PubMed1994

Lack of cardioprotective efficacy of allopurinol in coronary artery surgery.

OBJECTIVE: To examine the cardioprotective efficacy of allopurinol in patients undergoing elective coronary artery surgery. DESIGN: Prospective randomised trial. SETTING: London teaching hospital. PATIENTS: Twenty patients with at least moderately good left ventricular function undergoing elective coronary artery surgery and requiring at least two bypass grafts. INTERVENTIONS: Patients were randomised to receive allopurinol (1200 mg in two divided doses) or to act as controls. MAIN OUTCOME MEASURE: The primary determinant of the efficacy of myocardial protection was serial measurement (preoperatively and subsequently at one, six, 24, and 72 hours after the end of cardiopulmonary bypass) of cardiac troponin T (cTnT) a highly sensitive and specific marker of myocardial damage. Additional evidence was provided by serial measurement of the MB-isoenzyme of creatine kinase (CK-MB) and myoglobin, ECG changes, and clinical outcome. RESULTS: There was no significant difference in age, ejection fraction, number of grafts, bypass times, or cross clamp times between the two groups. In both groups there was a highly significant (p < 0.01) rise in cTnT, CK-MB, and myoglobin. Peak concentrations were reached between one (CK-MB and myoglobin) and six hours (cTnT) after the end of cardiopulmonary bypass. At 72 hours cTnT concentrations were six times higher than baseline concentrations whereas CK-MB and myoglobin were approximately double baseline concentrations. There was no significant difference in cTnT, CK-MB, or myoglobin between the allopurinol and control groups at any time. There was no diagnostic ECG evidence of perioperative infarction in any patient. CONCLUSION: Unlike previous reports this study did not show that allopurinol had a cardioprotective effect in patients with good left ventricular function undergoing elective coronary artery surgery.

Allopurinol↗
PubMed1994

Intermittent ischaemic arrest and cardioplegia in coronary artery surgery: coming full circle?

OBJECTIVE: To compare the cardioprotective efficacy of cold crystalloid cardioplegia and intermittent ischaemic arrest in patients undergoing elective coronary artery surgery. DESIGN: Prospective randomised trial. SETTING: London teaching hospital. SUBJECTS: 20 patients with at least moderately good left ventricular function undergoing elective coronary artery surgery by one experienced surgeon and needing at least two bypass grafts. INTERVENTIONS: Patients were randomised to cold crystalloid cardioplegia or intermittent ischaemic arrest. MAIN OUTCOME MEASURES: The primary determinant of the efficacy of myocardial protection was serial measurement (before and at 1, 6, 24, and 72 hours after the end of cardiopulmonary bypass) of cardiac troponin T (cTnT), a highly sensitive and specific marker of myocardial damage. RESULTS: There was no significant difference in age, ejection fraction, number of grafts, bypass times, or cross clamp times between the two groups. One patient in the cardioplegia group had a perioperative infarct and was excluded from further study. In both groups there was a significant increase in cTnT, with peak concentrations being reached 6 hours after the end of cardiopulmonary bypass and remaining significantly high at 72 hours. At 6 hours the median (75% interquartile range) concentrations of cTnT were similar in both groups (1.8 (1.0-3.6) micrograms/l for cardioplegia v 1.9 (1.0-3.5) micrograms/l for intermittent ischaemic arrest). CONCLUSION: This trial shows that intermittent ischaemic arrest, even without systemic cooling or venting of the left ventricle, provides a similar level of myocardial protection to cardioplegia in patients with moderate left ventricular function and short ischaemic times.

Coronary Artery Bypass↗
PubMed1994

Hyponatremic natriuretic syndrome in tuberculous meningitis: the probable role of atrial natriuretic peptide.

Hyponatremia has been reported in up to one third of patients with intracranial disease and has frequently been associated with tuberculous meningitis, often complicated by hydrocephalus. The lowered plasma sodium levels were previously attributed to the syndrome of inappropriate secretion of antidiuretic hormone. A controlled prospective study of 24 patients with tuberculous meningitis and hydrocephalus was carried out. Analyses of serum electrolytes and cerebrospinal fluid were performed. Plasma and cerebrospinal fluid levels of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured by radioimmunoassay. Fifteen patients were found to be hyponatremic (plasma sodium < 130 mmol/L) and ANP levels of 12 to 1,488 pg/ml were present (median, 26 pg/ml). The remaining 9 patients had normal plasma sodium values between 130 and 145 mmol/L, and in these, plasma ANP values varied between 12 and 21.7 pg/ml (median, 12 pg/ml). The difference between these two groups was not statistically significant. (Control values from patients undergoing myelography were established to range between 12 and 40 pg/ml; median, 14.4 pg/ml.) ANP levels were undetectable in the cerebrospinal fluid in all. Plasma ADH levels in the hyponatremic group were between 7 and 159 pg/ml (median, 40 pg/ml). In the normonatremic group, plasma ADH levels of 25 to 250 pg/ml (median, 29 pg/ml) were obtained. (The controls ranged between 3.6 and 35 pg/ml; median, 10.4 pg/ml). In the hyponatremic group, there was a moderate negative correlation (r = -0.683) between plasma ANP and plasma sodium (P = 0.02). No correlation between plasma ADH and plasma sodium was found (r = -0.168; P = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1994

Dichotomy in the human CD4+ T-cell response to Leishmania parasites.

Leishmania parasites cause human diseases ranging from self-healing cutaneous ulcers to fatal systemic infections. In addition, many individuals become infected without developing disease. In mice the two subsets of CD4+ T cells, Th1 and Th2, have different effects on the outcome of experimental Leishmania infections. Th1 cells producing interferon-gamma (IFN-gamma) mediate resistance, whereas Th2 cells producing interleukin-4 (IL-4) and IL-10 are associated with susceptibility and exacerbation. Evidence is accumulating that a Th1/Th2 dichotomy in the T-cell response to Leishmania exists also in humans, and that the balance between subsets of parasite-specific T cells may play an important regulatory role in determining the outcome of the infections.

Animals↗
PubMed1994

Long-term cyclosporin A nephrotoxicity in the rat. Evaluation of a morphological scoring system and of co-treatment with isradipine.

Cyclosporin A (CyA) nephrotoxicity was examined in Spraque-Dawley rats given CyA (12.5 (n = 45) or 25 (n = 45) mg/kg/day perorally for 16 weeks. Control rats (n = 45) received CyA vehicle. All rats were given either isradipine (ISRA) 1 or 5 mg/kg/day orally, or isradipine vehicle. Fifteen rats died from interstitial pneumonia caused by Staphylococcus xylosus. A predefined morphological CyA nephrotoxicity scoring system, based on semiquantitative scores for basophilic tubules and for interstitial fibrosis, performed on hematoxylin-eosin-stained tissue, yielded mean scores for basophilic tubules of 0.2 (range 0-1) in controls, 1.4 (range 0-3) in rats given CyA 12.5 mg/kg/day (p < 0.001), and 1.7 (range 0-3) in CyA 25 mg/kg/day rats (p < 0.001 as compared to controls). Rats given CyA were grouped according to their score for interstitial fibrosis: 0.2 (range 0-1) in CyA 12.5 mg/kg/day and 1.7 (range 0-3) in CyA 25 mg/kg/day rats (p < 0.001). When scores for basophilic tubules and interstitial fibrosis were pooled, none of the control rats had a score above 1, while 47% of the low-dose and 95% of the high-dose rats scored above 1. Thus, this CyA nephrotoxicity scoring system provided an easy, efficacious, and reproducible identification of rats with morphological CyA nephrotoxicity, and may be of clinical interest in the assessment of CyA nephrotoxicity. Kidney tissue from rats not treated with isradipine was further investigated with periodic acid-Schiff (PAS) with and without diastase treatment, and with Sirius Red. The latter confirmed the increase in connective tissue following tubular atrophy in CyA-treated rats. PAS reaction disclosed diastase-resistant positivity in the glomerular arterioles (score in controls: mean 0.4, range 0-1, in CyA 12.5 mg/kg/day mean 2.2, range 1-3, p < 0.001 as compared to controls; in CyA 25 mg/kg/day mean 1.1, range 0-2, p < 0.005 as compared to controls, p < 0.05 as compared to CyA 12.5 mg/kg/day). Furthermore, the straight part of the distal tubules of rats given the highest CyA dose contained considerable amounts of glycogen. The significance of this finding is unknown. Renal functional studies confirmed previous results since CyA decreased inulin clearance (Cin) from 1.2 +/- 0.5 to 0.8 +/- 0.3 ml/min/g kidney weight (kW) (p < 0.05), and lithium clearance (CLi) was reduced from 263 +/- 113 to 119 +/- 61 microliters/min/gKW (p < 0.001). Isradipine had no significant effect.

Animals↗
PubMed1993

Production of interferon-gamma and interleukin-4 by human T cells recognizing Leishmania lipophosphoglycan-associated protein.

The Leishmania protein LPGAP which is co-isolated with lipophosphoglycan is a specific activator of T cells from individuals who have recovered from American leishmaniasis. We have tested the effect of LPGAP on peripheral blood mononuclear cells (PBMC) from Kenyan donors cured from L. donovani infections. LPGAP induced vigorous proliferation and production of interferon-gamma (IFN-gamma) by the cells. In addition PBMC incubated with LPGAP released interleukin-4 (IL-4) after pulsing with ionomycin and phorbol myristate acetate. Single cells were isolated from LPGAP-stimulated cell lines and expanded as T-cell clones. LPGAP-reactive T-cell clones were activated by crude preparations of both promastigotes and axenic grown amastigote-like parasites. Among 9 CD4+ T-cell clones recognizing LPGAP, cells secreting predominantly IFN-gamma as well as cells secreting predominantly IL-4 were identified. The results show that both IFN-gamma producing (Th1-like) and IL-4 producing (Th2-like) T cells recognizing LPGAP are expanded after infection with L. donovani in humans.

Animals↗
PubMed1993

Interferon-gamma and interleukin-4 in human Leishmania donovani infections.

Clinical and immunological similarities between Leishmania donovani infections in humans and L. major infections in mice suggest that some of the pathophysiological mechanisms are the same in the two conditions. Both infections can result either in a fatal systemic disease or in a self-limiting infection with few and mild symptoms. In the murine model the outcome of the infection is critically related to the cytokines produced by T lymphocytes activated by leishmanial antigens. Activation of the IFN-gamma producing Th1 subset of CD4 positive T cells results in cure and survival, whereas activation of the IL-4 secreting Th2 subset results in a progressive disease with fatal outcome. A similar Th1/Th2 dichotomy in the cytokine response to L. donovani may exist in humans, and may have influence on the outcome of infection. In murine leishmaniasis the levels of IL-4 and IFN-gamma at the time of infection can direct the T cell response into Th1 or Th2 type. If similar mechanisms operate in humans, the outcome of L. donovani infections may depend on the local cytokine environment in which early activation of Leishmania specific T cells takes place. Cytokines secreted by cross-reactive memory T cells, activated by antigens from the invading micro-organism, may contribute to determine this environment.

Animals↗
PubMed1993

Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis.

Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.

Animals↗
PubMed1993

Prevalence of cutaneous leishmaniasis along the Nile River north of Khartoum (Sudan) in the aftermath of an epidemic in 1985.

Based on a pilot clinical study of the prevalence of cutaneous leishmaniasis (CL) among school children in villages on both banks of the Nile River north of Khartoum, Sudan in the aftermath of a 1985 epidemic, we studied a random sample (303 individuals) from one of these villages to determine the prevalence of infection and exposure to CL. Four percent of the population had active CL lesions, 47% had healed lesions, and another 43% reacted positively to sensitization with leishmanin in the absence of past or active CL lesions. Ninety-one percent of the total population reacted positively to leishmanin. The present status of CL in the area and possible reasons for the emergence of the epidemic are discussed, and gaps in our knowledge about the epidemic are identified.

Adolescent↗
PubMed1992

Recognition of Leishmania antigens by T lymphocytes from nonexposed individuals.

Crude antigen preparations of Leishmania promastigote sonicates were found to induce in vitro proliferation and gamma interferon production in peripheral blood mononuclear cells (PBMC) from individuals without known exposure to the parasite. The proliferating cells were mainly CD2-positive T cells. The proliferative response was maximal after more than 6 days of incubation with the antigens in contrast to the proliferation induced by the mitogenic lectin phytohemagglutinin (PHA), which peaked after 3 to 5 days. Judged by limiting dilution analysis, the frequencies of antigen-reactive precursor cells were less than 1:10,000 and varied considerably between individuals. Depletion of CD45R0-positive (memory) cells from the PBMC abolished proliferative responses induced by Leishmania antigen and by tetanus toxoid. In cell populations depleted of CD45RA-positive (naive) cells, only a small reduction in response was observed. Cell populations depleted of either CD45R0-positive cells or CD45RA-positive cells both responded to PHA. We conclude that presumably unexposed individuals have a low number of Leishmania-reactive T cells in their circulatory systems. The Leishmania-reactive T cells in these individuals are most likely memory cells recognizing antigens present both in the Leishmania preparations and in the environment.

Adult↗
PubMed1992

Antagonist capacity of felodipine on cyclosporin A nephrotoxicity in the rat.

Functional and morphological cyclosporin A (CsA) nephropathy has been attributed to a CsA-induced constriction of the afferent glomerular arteriole. Calcium-channel blockade with nifedipine prevented the development of short-term functional nephrotoxicity in CsA-treated rats. This study investigated whether the calcium antagonist felodopine, a structural analogue of nifedipine, which reduces renal tubular fractional sodium reabsorption, could prevent both short- and long-term functional and long-term morphological CsA nephropathy. In short-term experiments, four groups of Spraque-Dawley rats (n = 39) were given CsA (either 0 or 12.5 mg/kg per day by daily gastric intubation for 2 weeks), and felodipine (0 or 30 mg/kg per day) in the diet. In long-term experiments, rats (n = 39) were given CsA (12.5 mg/kg per day for 16 weeks), and felodipine (0 or 30 mg/kg per day in the diet). Renal function was investigated with clearance methods (inulin, lithium, and sodium), and kidney morphology was studied by light-microscopy. In short-term experiments, CsA treatment reduced GFR (730 versus 1181 microliters/min per g kidney weight (KW), P < 0.05) and CLi (130 versus 271 microliters/min per gKW, P < 0.02). Felodipine decreased proximal fractional reabsorption (PFR) (67.5% versus 71.4%, P < 0.05) and increased CNa (15.9 versus 8.4 microliters/min per gKW, P < 0.02) as compared to controls. In CsA-treated rats felodipine increased C in (1260 versus 730 microliters/min per gKW, P < 0.05) and CLi (319 versus 130 microliters/min per gKW, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1991

Activation of human T lymphocytes by Leishmania lipophosphoglycan.

This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon-gamma in vitro in response to lipophosphoglycan (LPG) isolated from Leishmania major. The proliferative response was mainly due to activation of CD2-positive T cells. PBMC from controls did not respond to LPG, but to sonicates prepared from both L. major and L. donovani promastigotes. The surface glycoprotein GP 63 failed to activate PBMC from any of the donors tested. These results show that the individuals cured from visceral leishmaniasis had expanded T-cell clones recognizing LPG, conceivably as a result of Leishmania infection. The LPG preparation was without detectable protein contamination. Thus, the results suggest that human T lymphocytes can respond to glycolipid antigens.

Animals↗
PubMed1989

Relationship between radiological classification and the serological and haematological features of untreated pulmonary tuberculosis in Indonesia.

Immunological and metabolic responses were studied in 110 patients with newly diagnosed pulmonary tuberculosis and 32 healthy controls from similar socioeconomic backgrounds. The severity of lung involvement was assessed radiologically, but this was not related to the current features of cell mediated immunity or to those of many aspects of the serological response to Mycobacterium tuberculosis. However, the patients with more extensive pulmonary tuberculosis showed higher titres of IgG2 antibody to whole killed M. tuberculosis and to the ML34 epitope shared by many species of mycobacteria. The patients with more extensive pulmonary tuberculosis showed a more marked metabolic response to infection as manifested by changes in serum levels of acute phase reactant proteins. Accordingly, the metabolic responses are considered to be more likely to prove of value in clinical monitoring of patients for severity of infection, or of reactivation of infection with M. tuberculosis, than immunological responses.

Acute-Phase Proteins↗
PubMed1988

Serial oxytocin levels in amniotic fluid and maternal plasma during normal and induced labour.

Oxytocin was measured by a specific and sensitive radioimmunoassay in plasma and amniotic fluid after extraction with Sep-Pak cartridges in patients undergoing elective caesarean sections, normal labour and labour induced with oxytocin infusion or prostaglandins. In maternal plasma, levels of oxytocin correlated with the period of gestation; concentrations at term were significantly higher than in the first two trimesters. Maternal plasma levels of oxytocin before the onset of contractions were not significantly different from those at the onset of spontaneous labour or at full cervical dilatation. Levels of oxytocin in patients induced with oxytocin were not statistically different from levels observed in spontaneous labour. Amniotic fluid oxytocin levels were not significantly different between the groups either at the onset of labour or immediately before delivery. Umbilical arterio-venous differences in oxytocin were present in all groups except the prostaglandin-induced group. Increased prostaglandins associated with the onset of normal labour are probably not a consequence of changes in oxytocin concentrations.

Amniotic Fluid↗