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Biomedical subjects

S Lucas

Publications and source records attributed to S Lucas.

At least 73 records · Page 4Linked to original sources

Acquired immunodeficiency syndrome and ocular calcification.

We report the presence of peculiar nonbanded calcification of the cornea in three patients with acquired immunodeficiency syndrome, discovered on postmortem histological examination of the globes. In one patient, multiple calcium salt precipitates also affected other ocular and orbital structures. Calcium deposits were present in the corneal stroma but spared Bowman's layer, as is usually seen in primary and secondary corneal calcification. The calcified areas were positive to von Kossa, alizarin red, alcian blue, and colloidal iron stains. Electron probe analysis of the three cases showed the presence of calcium and phosphorus in a ratio characteristic for hydroxyapatite. No predisposing factors could be found. The possible role of associated alterations in the mucopolysaccharide content or composition in the calcified areas is unclear.

Acquired Immunodeficiency Syndrome↗

The haemolytic uraemic syndrome in patients with AIDS.

OBJECTIVE: Thrombotic microangiopathies have been increasingly recognised in HIV infection. The contribution of haemolytic uraemic syndrome (HUS) has not received as much emphasis as other members of the thrombotic microangiopathies. We describe the clinical features and prognosis of HUS in a group of patients with AIDS. SETTING: St Bartholomew's and The Middlesex Hospitals, London. PATIENTS: Five HIV seropositive individuals with clinical and histological features consistent with HUS. INTERVENTIONS: Blood transfusion, fresh frozen plasma, haemodialysis, renal biopsy, autopsy. CONCLUSIONS: HUS occurs in advanced HIV infection. Hypertension was a prominent clinical feature in HUS in this patient group. Measures to limit renovascular damage were unsuccessful and haemodialysis was usually needed to support renal function. The prognosis is poor, no patient achieved clinical remission and all died.

Acquired Immunodeficiency Syndrome↗

[Rejection antigens of tumors and specific immunotherapy of cancer].

Human tumors carry antigens that are recognized by the patients' cytolytic T lymphocytes. An important group of antigens is coded by the MAGE family of genes. These antigens are expressed in a significant proportion of tumors of numerous histological types but not in normal tissues. Clinical trials are underway in an attempt to immunize patients suffering from metastatic melanomas using peptides coded by the MAGE genes. Regressions have been observed in 5 of the 17 immunized patients.

Antigens, Neoplasm↗

A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma.

Human melanoma MZ2-MEL expresses several distinct antigens that are recognized by autologous cytolytic T lymphocytes (CTL). Some of these antigens are encoded by genes MAGE-1, MAGE-3, and BAGE, which are expressed in a large fraction of tumors of various histological types but are silent in normal adult tissues with the exception of testis. We report here the identification of the gene coding for MZ2-F, another antigen recognized by autologous CTL on MZ2-MEL cells. This gene, which was named GAGE-1, is not related to any presently known gene. It belongs to a family of genes that are expressed in a variety of tumors but not in normal tissues, except for the testis. Antigenic peptide YRPRPRRY, which is encoded by GAGE-1, is recognized by anti-MZ2-F CTL on class I molecule HLA-Cw6. The two genes of the GAGE family that code for this peptide, namely GAGE-1 and GAGE-2, are expressed in a significant proportion of melanomas (24%), sarcomas (25%), non-small cell lung cancers (19%), head and neck tumors (19%), and bladder tumors (12%). About 50% of melanoma patients carry on their tumor at least one of the presently defined antigens encoded by the MAGE, BAGE, and GAGE genes.

Amino Acid Sequence↗

Individual differences in the orientation of the cytolytic T cell response against mouse tumor P815.

We reported previously that the mouse tumor P815 expresses four distinct antigens (A, B, C, D) recognized by syngeneic cytolytic T lymphocytes (CTL). A fifth P815 antigen (E) was identified by means of a CTL clone derived from tumor-infiltrating lymphocytes. We compared a number of mice for the orientation of their CTL response with respect to the various P815 antigens. Lymphocytes from mice inoculated subcutaneously with living P815 cells were stimulated in vitro with tumor cells and the resulting CTL were tested against targets expressing either antigens A and B or antigens C, D and E. Many mice had an asymmetrical response, some producing CTL directed almost exclusively against antigens A, B and others producing CTL directed almost exclusively against C, D. E. When mice were inoculated into two separate sites, different orientations in the responses of the two local lymph nodes were often observed, suggesting that individual differences in the orientation of the anti-P815 CTL response do not result from preexisting differences between the animals. Asymmetrical CTL responses persisted in mice that were given a second injection of tumor cells. A possible interpretation of our results is that the major component of the CTL response is made of the progeny of a very small number of CTL precursors that happen to be the first to be stimulated by the tumor antigens.

Amino Acid Sequence↗

The role of tyrosine phosphorylation in the interaction of cellular tyrosine kinases with the T cell receptor zeta chain tyrosine-based activation motif.

Immunoglobulin receptor family tyrosine-based activation motifs (ITAM) define a conserved signaling sequence, EX2YX2L/IX7YX2L/I, that mediates coupling of the T cell antigen receptor (TCR) to protein tyrosine kinases (PTK). In the present study, we explored the role of phosphorylation of the two ITAM tyrosine residues in the interactions of the motif with the PTK ZAP-70 and p59fyn. The data show that the phosphorylation of a single tyrosine within the motif enables binding of p59fyn, whereas phosphorylation of both tyrosines within the motif is required for maximal binding of the PTK ZAP-70. Quantitative binding experiments show that nanomolar concentrations of the doubly phosphorylated zeta 1-ITAM are sufficient for ZAP-70 recruitment, whereas micromolar levels of singly phosphorylated ITAM are necessary for p59fyn binding. ZAP-70 binds with low efficiency to a singly phosphorylated ITAM, but shows preferential binding to the C-terminal phosphotyrosine in the ITAM, whereas p59fyn binds selectively to the N-terminal phosphotyrosine. The present data thus show that there is the potential for a singly phosphorylated ITAM to couple to cellular PTK. Moreover, the data suggest a mechanism for heterogeneity in signal transduction responses by the TCR, since ITAM could differentially couple the TCR to downstream signaling events depending on their phosphorylation state.

Amino Acid Sequence↗

A patient with autoimmune thrombocytopenic purpura demonstrating serum antibodies reactive with mouse cross-reactive idiotypes.

Autoimmune thrombocytopenic purpura (ATP) is a syndrome of destructive thrombocytopenia due to platelet-binding antibodies. We report the case of a young woman (C.V.) who has a history of chronic ATP with severe but transient bouts of thrombocytopenia. Using the classic monoclonal antibody (MAb) immobilization of platelet antigens (MAIPA) assay to screen serum antibody specificity, results were strongly positive with MAbs to glycoproteins (GPs) Ib-IX, Ia-IIa, IV, and p24, but weakly positive or negative for GP IIb-IIIa. In contrast, a two-step incubation assay (MAIPA II), in which platelets were incubated sequentially with C.V. serum and the murine MAb, gave negative results for all GPs. Affinity chromatography performed using Bx-1, a MAb to GP Ib, showed that the patient's serum contained antibodies to determinants expressed by mouse immunoglobulins. These were present on Fab fragments on Bx-1. A survey of sera from other patients with thrombocytopenia of immune origin revealed that antibodies reactive with selected idiotypes of mouse MAbs were not infrequent and raises the question of their role in the thrombocytopenia.

Adult↗

Autopsy-proven causes of death in HIV-infected patients treated for tuberculosis in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine autopsy-proven causes of death in HIV-infected patients treated for tuberculosis in Abidjan, Côte d'Ivoire. METHODS: A computerized listing of 9523 patients diagnosed with tuberculosis and tested for HIV infection at Abidjan's two large tuberculosis treatment centers from July 1989 to December 1991 was matched against a listing of 496 patients who were autopsied in Abidjan's largest public hospital in 1991-1992. RESULTS: Fifteen matching patients were identified including 11 adults with smear-positive pulmonary tuberculosis, three adults with extrapulmonary tuberculosis, and one child with smear-negative pulmonary tuberculosis. The autopsy-proven causes of death among the adults were tuberculosis (n = 4), bacterial infections (n = 3), cerebral toxoplasmosis (n = 2), pulmonary nocardiosis (n = 2), Pneumocystis carinii pneumonia (n = 1), atypical mycobacteriosis (n = 1), and wasting syndrome (n = 1). Tuberculosis was the primary cause of death in two of five smear-positive patients who had not completed therapy, in none of the six patients with smear-positive disease who had completed therapy, and in two of the three patients with extrapulmonary tuberculosis. CONCLUSIONS: Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) might have provided benefit to eight (57%) of the 14 adults in this series who died either of bacterial infections, toxoplasmosis, nocardiosis, or pneumocystosis. Prospective studies are required to elucidate further the causes of increased mortality, and to evaluate the benefits of TMP-SMX prophylaxis in HIV-infected African patients with tuberculosis.

Adult↗

Histological study of oxalosis in the eye and adnexa of AIDS patients.

Review of a series of 98 eyes removed at autopsy from 86 AIDS patients identified 12 cases (14%) showing varying degrees of microscopic calcium oxalate deposition. The oxalate crystals were birefringent using polarisation microscopy and were stained histochemically by the silver nitrate-rubeanic acid method (Yasue), a stain considered to be specific for calcium oxalate. In two cases, the deposition was extensive and involved the surface of the ciliary processes, ciliary body and pars plana of the retina, the retinal and optic nerve blood vessel wall, a few retinal pigment cells, and the anterior inner sclera. A lesser degree of intraocular involvement was observed in the remaining 10 cases. In all but two eyes, where a peripheral active area of cytomegalovirus retinitis was present, no other significant microscopical abnormality was found. Clinically, these patients were asymptomatic. At autopsy, oxalate deposits were found in the kidney and/or thyroid in seven of the patients.

Acquired Immunodeficiency Syndrome↗

[Autopsy findings in 70 AIDS patients who died in a department of pneumology in Ivory Coast: impact of tuberculosis].

Based on autopsy findings in 70 patients infected by human immunodeficiency virus (HIV) who died in the Pulmonology Department of the Treichville University Hospital Center in Abidjan, Ivory Coast. the authors assess the incidence of tuberculosis as the cause of death and analyze the clinical, bacteriologic, and histologic features of the disease. in this population. Pulmonary tuberculosis was the first cause of death in this series accounting for 31 cases (44.2%). In 12 cases (38.7%), microscopic identification failed during hospitalization and the disease had been misdiagnosed as common bacterial pneumonia. In 29 cases (93.5%) pulmonary tuberculosis was associated with abdominal involvement. In 17 cases (54.8%) involvement of more than two organs was observed. Of the 60 abdominal sites detected during the autopsy of the 31 patients with pulmonary tuberculosis, there were 19 (31.3%) in lymph nodes, 18 (30%) in the liver, 14 (23.3%) in the spleen, and 9 (14.9%) in the kidneys. Histologic features were remarkable by the absence of typical tuberculous granulomas. The findings of this study confirm the high incidence of disseminated tuberculosis in patient infected by HIV as noted in a number of previous studies.

AIDS-Related Opportunistic Infections↗

Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a retrospective study of 37 cases.

OBJECTIVES: To study the demographic, clinical, radiographic and diagnostic features, the clinical course and therapeutic response of pulmonary cryptococcosis in HIV-1-infected patients. DESIGN: Retrospective review. SETTING: The Department of Medicine of an urban reference hospital in Central Africa. METHODS: All the records of HIV-1-infected patients with pulmonary cryptococcosis were reviewed retrospectively with regard to the parameters described above. RESULTS: Over a 3-year period, pulmonary cryptococcosis was diagnosed in 37 HIV-1-infected Rwandan patients (21 men, 16 women; mean age, 35 years; range, 26-55 years). Twenty-nine patients (78%) had primary pulmonary cryptococcosis. Cough (94%), weight loss (65%), fever (51%), dyspnoea (46%), thoracic pain (30%), headache (13%) and haemoptysis (8%) were the predominant clinical findings. A diffuse interstitial infiltrate on chest radiograph was observed in 76% of the patients, an alveolar pattern in 19%, mediastinal and/or hilar adenopathy in 11%, nodules and pleural effusion each in 5%. Bronchoalveolar lavage, with a yield of 82%, was found to be the most sensitive diagnostic procedure. Screening of cryptococcal antigen in the serum failed to detect cases of primary pulmonary cryptococcosis. Twelve patients with primary pulmonary cryptococcosis treated with itraconazole as acute and maintenance therapy were all protected against disseminated cryptococcal disease; seven out of 10 (70%) of those who did not receive a specific anticryptococcal drug developed disseminated cryptococcal disease. CONCLUSION: Pulmonary cryptococcosis is not a rare complication of HIV-1 infection in Rwanda. Its clinical and radiographic patterns are non-specific and bronchoalveolar lavage is the procedure of choice for its diagnosis. The natural history of untreated primary pulmonary cryptococcosis is disseminated cryptococcal disease. Itraconazole is highly effective in the prevention of disseminated cryptococcal disease in patients with primary pulmonary cryptococcosis.

AIDS-Related Opportunistic Infections↗

Pulmonary disease associated with the human immunodeficiency virus in Kigali, Rwanda. A fiberoptic bronchoscopic study of 111 cases of undetermined etiology.

All human immunodeficiency virus type 1 (HIV-1) infected adult patients referred to the Division of Pulmonary Diseases of the Centre Hospitalier de Kigali, Rwanda for evaluation of a pulmonary disease of undetermined etiology (PDUE) were investigated by fiberoptic bronchoscopy using both bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB). During a 10-mo period 111 HIV-1 infected patients with PDUE were examined, of whom 47 (42%) fulfilled the World Health Organization (WHO) clinical case definition for acquired immunodeficiency syndrome (AIDS) and seven (6%) had an AIDS-defining illness. Nonspecific interstitial pneumonitis was diagnosed in 42 (38%) patients, tuberculosis in 25 (23%), cryptococcosis in 14 (13%), Kaposi's sarcoma (KS) in 10 (9%), Pneumocystis carinii pneumonia (PCP) in five (5%). The diagnosis remained undetermined in 18 (16%) patients. Chest radiograph patterns were generally nonspecific. TBB and BAL had diagnostic yields of 82 and 26% of all final diagnoses, respectively. Our study on Rwandese HIV-1-infected patients with PDUE provides evidence for a large spectrum of pulmonary diseases with relative frequencies differing strikingly from those in developed countries. Detailed investigations confirm the rarity of PCP in Africa and highlight nonspecific interstitial pneumonitis as the predominant diagnosis of PDUE. Empiric antituberculosis treatment is justified in the absence of clinical manifestations suggestive of a specific diagnosis and while awaiting the results of the diagnostic procedures. Primary prophylaxis for PCP would not be appropriate in Africa.

Adult↗

Episodic brainstem compression masquerading as electrodecremental seizures.

An 8-year-old boy developed generalized tonic spasms lasting minutes accompanied by an electrodecremental event on electroencephalogram in association with increased intracranial pressure caused by shunt malfunction. The electroencephalographic abnormalities and clinical attacks occurred despite an otherwise normal neurologic examination, normal initial opening pressure on lumbar puncture and shunt tap, and only mild ventricular dilation revealed by brain imaging. There was no improvement with antiepileptic drugs. Further signs of uncal herniation led to repeat tap of the shunt, revealing a pressure of 800 mm of water. After revision of the shunt "seizures" stopped and the electroencephalogram returned to normal. Antiepileptic drugs were discontinued, with no recurrence of events.

Brain Stem↗

[Prevalence of pneumocystosis in HIV infected patients in a pneumology unit. Autopsy study performed in Abidjan (Côte d'Ivoire)].

Autopsies were performed in the Pathology Department of the Treichville University Hospital, Abidjan, Ivory Coast in 70 HIV infected subjects who had died in the Department of Pneumophtisiology. The prevalence of Pneumocystis carinii pneumonia was determined. None of the patients had received prophylaxis against P. carinii and none had bee treated for pneumocystosis. Autopsies were performed within 6 to 48 hours after death and the diagnosis of pneumocystosis was confirmed with the Gomori-Grocott staining technique on lung specimens. Among the 70 autopsies Pneumocystis carinii pneumonia was observed in 6. Thus the prevalence of P. carinii pneumonia in these patients infected with HIV was 8.57%.

AIDS-Related Opportunistic Infections↗