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Biomedical subjects

S Lucas

Publications and source records attributed to S Lucas.

At least 91 records · Page 5Linked to original sources

The genomic region encoding toxin gamma from the scorpion Tityus serrulatus contains an intron.

The gene encoding toxin gamma from the scorpion, Tityus serrulatus, was amplified by PCR from genomic DNA employing synthetic oligonucleotides designed from the reported cDNA sequence. The nucleotide sequence of this gene reveals the presence of an intron of 475 base pairs (bp) which interrupts the region that encodes the signal peptide of the precursor toxin. A comparison of the intron boundary sequences of the gamma toxin gene with ones from other arachnid genes is also presented.

Animals↗

Macrophage nitric oxide synthase subunits. Purification, characterization, and role of prosthetic groups and substrate in regulating their association into a dimeric enzyme.

The cytokine-induced nitric oxide synthase (NOS) of macrophages is a homodimeric enzyme that contains iron protoporphorin IX (heme), FAD, FMN, tetrahydrobiopterin, and calmodulin. To investigate how the enzyme's quaternary structure relates to its catalytic activity and binding of prosthetic groups, dimeric NOS and its subunits were purified separately and their composition and catalytic properties compared. In contrast to dimeric NOS, purified subunits did not synthesize NO or contain bound heme or tetrahydrobiopterin. However, the subunits did contain FAD, FMN, and calmodulin in amounts comparable with dimeric NOS, displayed the light absorbance spectrum of an FAD- and FMN-containing flavoprotein, and generated an air-stable flavin semiquinone radical upon reduction of their ferricyanide-oxidized form. Dimeric NOS and NOS subunits were equivalent in catalyzing electron transfer from NADPH to cytochrome c, dichlorophenolindophenol, or ferricyanide at rates that were 8-30-fold faster than the maximal rate of NO synthesis by dimeric NOS. Reconstitution of subunit NO synthesis required their incubation with L-arginine, tetrahydrobiopterin, and stoichiometric amounts of heme and correlated with formation of a proportional amount of dimeric NOS in all cases. The dimeric NOS reconstituted from its subunits contained 0.9 heme and 0.44 tetrahydrobiopterin bound per subunit and had the spectral and catalytic properties of native dimeric NOS. Thus, NOS subunits are NADPH-dependent reductases that acquire the capacity to synthesize NO only through their dimerization and binding of heme and tetrahydrobiopterin. The ability of heme, tetrahydrobiopterin, and L-arginine to promote subunit dimerization is unprecedented and suggests novel roles for these molecules in forming and stabilizing the active dimeric NOS.

Amino Acid Oxidoreductases↗

Diarrhoea associated with cyanobacterium-like bodies: a new coccidian enteritis of man.

Faecal excretion of cysts known as cyanobacterium-like bodies (CLB) is associated with a diarrhoeal illness, which is often prolonged and severe. It is seen mainly in travellers and immunocompromised patients. Recently these cysts have been shown to be coccidian oocysts. We describe three patients who developed diarrhoea while travelling abroad. Stool samples from all three patients contained CLB. Jejunal aspirates from two patients also yielded CLB. Conventional histology of jejunal biopsy specimens confirmed that two patients had enteritis. Electronmicroscopy of the same biopsy specimens revealed intraepithelial coccidia. These findings suggest that the small bowel is the site of infection of this new coccidian disease.

Adult↗

Bcl-2 proto-oncogene expression in Epstein-Barr-virus-associated nasopharyngeal carcinoma.

The bcl-2 proto-oncogene product inhibits apoptosis. Increased levels of bcl-2 protein are associated with prolonged B-cell survival and have been demonstrated in a high proportion of follicular B-cell lymphoma. Recent studies have shown that bcl-2 protein expression in B cells immortalized by Epstein-Barr virus (EBV) in vitro is up-regulated by the EBV-latency-associated antigen, latent membrane protein (LMP) 1. The epithelial malignancy, undifferentiated nasopharyngeal carcinoma (UNPC), has a well-established association with EBV and the tumour cells characteristically display a restricted latent viral phenotype including LMP 1. This study has investigated the relationship between the presence of EBV DNA, EBV phenotypic profiles and bcl-2 protein expression in conventionally processed and cryopreserved samples of NPC using in situ hybridization, immunocytochemical and immunoblotting techniques. bcl-2 was detected in most (80%) samples of UNPC as well as in 1/3 samples of keratinizing NPC and 2/2 samples of nasopharyngeal adenocarcinoma. However, no close correlation was found between the presence of EBV DNA, and profiles for LMP 1 and bcl-2 protein expression in 45 UNPC. In addition, bcl-2 protein was shown to be selectively expressed in the basal compartment of normal nasopharyngeal epithelia. bcl-2 protein expression has not been reported previously in malignant tumours of epithelial origin. The findings in this study implicate a role for bcl-2 both in normal keratinocyte differentiation and in the pathogenesis of epithelial malignancy.

Adenocarcinoma↗

Multiple cerebral hemorrhages in HTLV-I-associated myelopathy.

We describe a 66-year-old woman with long-standing HTLV-I-associated myelopathy who developed multiple parenchymal hemorrhages and whose angiogram suggested cerebral vasculitis. After cyclophosphamide and glucocorticoid therapy, both her acute deficits and chronic paraparesis improved. HTLV-I may be an etiologic agent in isolated angiitis of CNS.

Aged↗

Clinical research, prophylaxis, therapy, and care for HIV disease in Africa.

By the end of the century, citizens of resource-poor countries will constitute 90% of the world's human immunodeficiency virus (HIV)-infected people. Clinical management of such persons in developing countries has been neglected; most AIDS research has concentrated on epidemiology, and donor agencies have generally invested in the prevention of HIV infection. The heavy burden of HIV disease in Africa requires that care for AIDS be addressed, and prevention and care should be seen as interrelated. Prevention and treatment of tuberculosis, the commonest severe infection in persons with AIDS in Africa, illustrate this interrelationship. We outline priorities for applied research on the management of HIV disease in a resource-poor environment, and discuss prophylaxis, therapy for opportunistic diseases, terminal care, and use of antiretroviral therapy. Research should define the standard of care that can realistically be demanded for HIV disease in a resource-poor environment. Research and public health programs for AIDS in developing countries must address AIDS care and attempt to reduce the widening gap between interventions available for HIV-infected persons in different parts of the world.

AIDS-Related Opportunistic Infections↗

Human immunodeficiency virus and leprosy.

In summary, clinical leprosy does not appear to be more frequent in HIV-positive than in HIV-negative people in areas where both infections are endemic. There is no evidence that the paucibacillary to multibacillary distribution of patients is altered by HIV infection. There are reports that neuritis is more severe in co-infected people, and that reversal reactions (or, at least, new lesions) may be more frequent after therapy; but these reports are either poorly documented or poorly controlled. In several ways, this lack of expected leprosy is similar to the patterns of other low-virulent infections in HIV-positive patients in the tropics, such as MAC infection, Pneumocystis carinii and cytomegalovirus infection. Despite the presence of the agents in the environment and/or in the human host, they are infrequently encountered clinicopathologically. This is in marked contrast to their importance in industrialized countries. One explanation, as yet unproven, is that HIV-positive patients in the tropics do not live long enough in states of severe immunosuppression to develop these infections. Perhaps the same applies to M. leprae infection, whose incubation period can be measured in decades and whose clinical course may evolve over years, in contrast to the common reactivation of latent, virulent M. tuberculosis infection with its high morbidity. There may also be an analogy between leprosy and infection with Plasmodium falciparum, Strongyloides stercoralis and Entamoeba histolytica: these infections are controlled (or at least influenced) by cell-mediated immunity and, theoretically, should be more frequent in HIV-positive people than HIV-negatives. In fact they are not, and leprosy may be regarded as another 'missing infection in AIDS'.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV Infections↗

[Pulmonary diseases and retrovirus infections. A pathological study in 70 cases].

A necroscopic study, conducted in the Pathology Department of the Centre Hospitalier Universitaire (CHU) de Treichville in Abidjan, included 70 seropositive subjects who died in the Pneumophtisiology Department. We attempted to determine the different pulmonary affections occurring during infection with the human immunodeficiency virus (HIV). This study demonstrated the predominant role of tuberculosis (44%) and bacterial pneumonia (30%) which remain the predominant aetiologies. Other opportunistic affections were rare including: Pneumocystises, Mycobacteriaceae, and Cytomegalovirus infection and the Kaposi sarcoma. The absence of pulmonary cryptococcosis and non-Hodgkin lymphoma were also noted. Necroscopic examinations do not necessarily provide evidence of the in vivo pathologies, the autopsy being able to identify only the causal diseases or those present at death.

AIDS-Related Opportunistic Infections↗

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↗