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Biomedical subjects

S Lucas

Publications and source records attributed to S Lucas.

At least 19 recordsLinked to original sources

Glutamatergic postsynaptic block by Pamphobeteus spider venoms in crayfish.

The effects of toxins from venom glands of two south american spiders (Pamphobeteus platyomma and P. soracabae) on glutamatergic excitatory synaptic transmission were studied in the neuromuscular junction of the opener muscle of crayfish. The toxins selectively and reversibly blocked both excitatory postsynaptic currents and potentials in a dose-dependent manner. They also reversibly abolished glutamate-induced postsynaptic membrane depolarization. They had no effect on resting postsynaptic membrane conductance nor on postsynaptic voltage-gated currents. The synaptic facilitation and the frequency of miniature postsynaptic potentials were unaffected by the toxins, indicating that presynaptic events were not modified. Picrotoxin, a selective antagonist of the gamma-aminobutyric acid (GABA)A receptor, did not modify toxin effects. We conclude that both toxins specifically block the postsynaptic glutamate receptor-channel complex.

Animals

T lymphocyte activation signals.

Activation of T lymphocytes results in immediate biochemical changes including increases in intracellular calcium levels, activation of protein kinase C (PKC) and changes in tyrosine phosphorylation. In T cells recent studies have indicated that activation of the guanine nucleotide-binding proteins p21ras is mediated by PKC, which suggests that the p21ras proteins may regulate intracellular signalling events downstream of PKC. The p21ras proteins can be activated in T cells by signals generated by triggering of the T cell antigen receptor (TCR), the CD2 antigen and the interleukin 2 receptor. Experiments using a PKC pseudosubstrate inhibitor indicate that PKC does not mediate TCR-induced activation of p21ras. These results imply that an alternative signal transduction pathway not involving PKC can regulate the activity of p21ras proteins in T cells.

Humans

The pathology of the posterior root ganglia in AIDS and its relationship to the pallor of the gracile tract.

The spinal cord and the thoracic and lumbar posterior root ganglia (PRGs) of 14 HIV-positive men and 7 age- and sex-matched controls were studied by routine histology, morphometric analysis of the number of nodules of Nageotte (nN) and the diameters of sensory ganglion cells, immunohistochemistry and in situ hybridization. In 7 patients (2 of whom had evidence of cytomegalovirus ganglionitis) there were increased numbers of nN and diffuse, mild infiltration with CD45R+ T lymphocytes; no B lymphocytes were observed. Macrophages were increased in number in all cases. Whenever more than one ganglion was examined from the same patient, the appearances were similar in all. There was no alteration in the distribution of ganglion cell diameters. Changes in the spinal cord included vacuolar myelopathy (5 cases), HIV myelitis (1 case), microglial nodules (3 cases) and pallor of the gracile tracts (GTP) in 7 cases, in 6 of whom it co-existed with increased numbers of nN. Seven cases had no abnormalities, except the increase in number of macrophages in PRGs. In spite of a correlation between sensory nerve cell loss and GTP our findings suggest that other mechanisms, such as 'dying back' may contribute to the pathogenesis of GTP. Moreover, sensory disturbances were found most commonly in association with nerve cell loss; however, loss of sensory ganglion cells was not necessarily associated with evidence of sensory impairment.

Acquired Immunodeficiency Syndrome

Hairy leukoplakia.

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HIV Seropositivity

Histoplasmosis of the central nervous system.

Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed.

Adrenal Glands

Pneumocystis carinii pneumonia. An uncommon cause of death in African patients with acquired immunodeficiency syndrome.

Admissions and deaths in a pulmonary medicine ward in Abidjan, Cote d'Ivoire, West Africa, were evaluated over a 6-month period in 1989 with systematic autopsies on all patients who died. Of 473 patients admitted, 38% were HIV-1 seropositive, 4% were HIV-2 seropositive, and 14% reacted to both viruses. A total of 100 patients (21%) died, and deaths were twice as frequent in HIV-seropositive compared with HIV-negative patients. The pathology of 78 autopsies showed that the predominant cause of death in HIV-seropositive patients was disseminated tuberculosis (40%). Cancer was the cause of death in 64% of HIV-negative patients. Pneumocystosis was found in only 9% of HIV-seropositive autopsies. Since Pneumocystis carinii is an uncommon cause of death in this population, prophylaxis for P. carinii pneumonia is not warranted for HIV-infected patients in Africa. In contrast, research on chemoprophylaxis for tuberculosis is urgently required.

Acquired Immunodeficiency Syndrome

[Asymptomatic giant thoracic dumbbell neurinoma. Apropos of a case].

Giant thoracic dumbbell neurinomas are usually revealed by neurological or mediastinal signs. The case we are reporting was discovered accidentally and allow us to add some accuracy to the current diagnostic criteria for these tumors. MRI provides the most interesting information. The surgical exeresis of these tumors must use a double approach: first laminectomy then thoracotomy.

Adult

Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis.

The effects of the human immunodeficiency virus (HIV) on tuberculosis management was investigated in 227 patients initially treated with a regimen containing streptomycin, isoniazid, and thiacetazone (STH). 93 of these 227 were HIV-seropositive. 60 patients, of whom 18 were HIV-seropositive, received a regimen consisting of streptomycin, isoniazid, rifampicin, and pyrazinamide (SHRZ) in the initial phase, and thiacetazone and isoniazid (TH) in the continuation phase. Cutaneous hypersensitivity reactions occurred in 22 of 111 (20%) HIV-seropositive patients, and in 2 of 176 (1%) HIV-seronegative patients (RR = 18, 95% CI 4.4-76, p less than 10(-7]. During the first 8 weeks of treatment 18 reactions occurred among the 93 HIV-seropositive patients on STH, whereas no reaction occurred in 17 HIV-seropositive patients during the initial phase of SHRZ/TH (p = 0.04). None of the 18 HIV-seropositive patients with cutaneous reactions who were subsequently challenged with isoniazid reacted, nor did any of the 10 tested with streptomycin, but 6 of the 7 challenged with thiacetazone reacted. 3 patients (all HIV-positive and with toxic epidermal necrolysis) died as a result of the cutaneous reaction. These results have major implications for tuberculosis control programmes in Africa.

Adult

Crisnatol mesylate: phase I dose escalation by extending infusion duration.

Crisnatol mesylate is a rationally designed cytotoxic arylmethylamino-propanediol with broad spectrum cytotoxic activity. A phase I study with an unconventional escalation scheme was developed using a constant drug infusion rate (mg/m2/hr) and prolonging the infusion duration from 6 to 96 hours. Sixty-five patients received crisnatol at doses from 18 mg/m2 in 6 hrs to 3400 mg/m2 in 72 hours. The dose-limiting toxicity in two of five patients at 2700 mg/m2 and two of three patients at 3400 mg/m2 was neurologic and consisted of a syndrome of confusion, agitation, and disorientation. Phlebitis mandated the use of a central line. The mean terminal phase half-life (T1/2 beta) was 3.3 hours with a total body clearance (CL) of 22.8 L/hr/m2 and a volume of distribution (Vdss) of 53 L/m2. The median steady-state peak plasma concentration (Css) at 2700 mg/m2/72 hours was 2.7 micrograms/ml and at 3400 mg/m2/72 hours was 3.8 micrograms/ml. No responses were seen. The maximum tolerated dose (MTD) on this schedule is 2700 mg/m2/72 hours in patients with no liver disease and good performance status.

Adolescent

pH dependence of hydrochloric acid diffusion through gastric mucus: correlation with diffusion through a water layer using a membrane-mounted glass pH electrode.

Solute diffusion coefficients (D) can indicate a dependence upon actual solute concentrations. Here a single compartment has been utilized, in which effective HCl diffusion to a membrane-mounted glass pH electrode can be measured across the pH spectrum. The study has investigated HCl diffusion through both mucus and water layers as a function of HCl concentration. The observed dynamic responses of a liquid-film and mucus-coated electrodes over a range of HCl concentrations suggest that the speed at which equilibrium is attained is pH dependent; equilibrium was reached rapidly under more acidic and alkaline conditions. Estimated values of DHCl also indicate a strong pH dependence for both liquid film and mucus. In both instances, a greater than 10-fold reduction in DHCl at pH 7.5 as compared with that at pH 3.5 has been demonstrated. Furthermore, estimated values of DHCl are approximately 4-fold smaller through the mucus gel, as compared with a water layer. The findings indicate that the most powerful influence on diffusional resistance is pH itself, whereby a marked drop in H+ diffusion is likely to occur towards neutral pH irrespective of the composition of the gel barrier. Possible implications of the findings are discussed in relation to mucosal protection from acid.

Animals

Altered small-intestinal permeability associated with diarrhoea in human-immunodeficiency-virus-infected Caucasian and African subjects.

1. Small-intestine integrity in Caucasian and African patients infected with human immunodeficiency virus was determined by measuring the permeation across the mucosa of two sugars, lactulose and mannitol. 2. The sugars were assayed by h.p.l.c. and pulsed amperometric detection in 6 h urine samples. Stool microscopy for enteropathogens was performed in all patients. 3. The ratio of lactulose to mannitol recovered in urine was increased in Caucasian and African patients with advanced human immunodeficiency virus infection. Asymptomatic human-immunodeficiency-virus-infected subjects had a normal lactulose/mannitol ratio. African patients with diarrhoea showed a twofold reduction in mannitol excretion. Such a change in mannitol absorption was not detected in Caucasian patients and occurred regardless of the presence of enteropathogens. 4. Altered small-intestinal permeability is associated with symptomatic diarrhoea in human immunodeficiency virus infection in both Caucasian and African patients.

Adult

Sex differences in gallstone pancreatitis.

From a computerized database comprising 28 pertinent items in each of a consecutive series of 664 patients with cholelithiasis, differences were studied between men and women. In 52 patients there was a documented attack of acute pancreatitis (7.8%). Twenty-five of 174 men had pancreatitis, compared with 27 of 490 women (p less than 0.0001). Men developed gallstones later in life than women, but suffered gallstone pancreatitis earlier in life and in the course of their gallstone-related disease. A history of flatulent dyspepsia, chronic cholecystitis, and biliary colic was less common in men than in women with pancreatitis (p less than 0.0001). Men with pancreatitis had fewer stones in their gallbladders than did women (p = 0.0002). The cystic duct and the common bile duct in the pancreatitic patient were more likely to be dilated (p less than 0.0001). In the nonpancreatic group, these ducts were larger in men. Pancreatic duct reflux on operative cholangiography was more common both in patients with pancreatitis 62% cf 14% (p less than 0.0001), and in men (p less than 0.001). Predisposition to pancreatitis relates to duct size rather than stone size per se. Men are more susceptible to gallstone migration at an early stage of their disease. In addition they have a larger diameter duct system and possibly a different anatomic disposition of the sphincter of Oddi, which predisposes them to a higher incidence of pancreatitis than women. The data suggest that it is cystic duct size that is critical in the pathogenesis of gallstone pancreatitis.

Acute Disease

Heterogeneity of protein kinase C expression and regulation in T lymphocytes.

The purpose of the present study was to examine protein kinase C (PKC) isotype expression in T lymphoblasts derived from peripheral blood and the T leukaemic cell Jurkat. Using antisera reactive with PKC alpha, beta 1, and beta 2 and gamma, it was observed that T cells expressed two PKC isotypes, PKC alpha and beta 1. No PKC gamma was detected in T lymphocytes. In lymphoblasts, high levels of PKC beta compared to PKC alpha were found whereas Jurkat cells expressed high levels of alpha compared to PKC beta. Differences in the calcium sensitivity of phorbol ester-induced phosphorylation were observed in Jurkat and T lymphoblasts which correlated with the relative levels of PKC alpha and beta isotypes expressed by the cells.

Antigens, Differentiation, T-Lymphocyte

The involvement of the cerebral cortex in human immunodeficiency virus encephalopathy: a morphological and immunohistochemical study.

The encephalopathy resulting from direct infection of the brain by human immunodeficiency virus (HIV), which correlates clinically with the AIDS dementia complex, has been reported as being localized to the white matter where it induces myelin loss, gliosis and perivascular infiltration by mononuclear macrophages and multinucleated giant cells. Damage to the cortical grey matter in HIV encephalopathy was investigated in nine randomly selected HIV-positive cases with or without clinical or morphological evidence of encephalopathy and in five age-matched controls, using routine histology and immunohistochemical methods [glial fibrillary acidic protein (GFAP), microglia and HIV antibodies]. Increased numbers of GFAP-expressing astrocytes and Ricinus communis agglutinin 1-120-expressing microglial cells were found in all the HIV-positive cases (including asymptomatic) and their severity could be correlated with the severity of the encephalopathy in the white matter; the increase in number of cells expressing GFAP was diffuse and the intensity of the staining higher than that of microglial cells. The subpial region was the most severely involved. It is suggested that involvement of the cortical grey matter is more common in HIV infection than previously suspected and that clinical evidence of a dementing process in AIDS is not necessarily due only to white matter lesions.

AIDS Dementia Complex