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Biomedical subjects

A Valentin

Publications and source records attributed to A Valentin.

At least 109 records · Page 6Linked to original sources

[Multiple cerebrovascular lesions as fatal late sequelae of syphilis].

A previously healthy man, aged 33 years, suddenly developed a hemiparesis and right facial paresis, as well as anisocoria and motor aphasia, preceded by recurrent attacks of dizziness. On admission he was somnolent. A flow murmur was heard over both carotid arteries; the blood pressure was 160/80 mm Hg. Cerebral computed tomography demonstrated multiple hypodense areas in the area supplied by several cerebral arteries, and marked cerebral oedema. Angiography of the aortic arch and the supra-aortic branches showed an occlusion of the left common carotid artery and a stenosis of the brachiocephalic trunk. The cerebral oedema, caused by ischaemia, did not respond to treatment. The patient died on the fourth hospital day from brainstem "strangulation". At autopsy syphilitic mesaortitis with characteristic lymphoplasmacellular endangiitis of the vasa vasorum of the aortic arch was demonstrated as the cause of the "aortic arch syndrome". Serology confirmed the diagnosis of an untreated tertiary syphilis. (VDRL titre 1:256; TPHA reactive; IgM-SPHA titre 1:64). Although a very rare cause, a late stage of syphilis should be considered in the differential diagnosis of cerebrovascular lesions in youngish patients.

Adult↗

Lipid trafficking between high density lipoproteins and Babesia divergens-infected human erythrocytes.

A two-fold increase in the amount of phospholipids was observed in Babesia divergens infected human red blood cells. In vitro incubation with [32P]-phosphorus and [3H]-glycerol demonstrated that B divergens has the ability to synthesize the phospholipid backbone. On the other hand, the low incorporation of [14C]acetate indicated the absence of a de novo fatty acid synthesis and suggested the necessity of an exogenous lipid source for the parasite. Several intra-erythrocytic growth cycles of B divergens could be achieved in vitro, using a serum-free medium supplemented only with fractions of human high density lipoproteins (HDL). At an HDL concentration of 0.5 mg/ml (protein concentration) and with a 1% starting parasitaemia, parasite growth was similar to that observed under standard culture conditions with 10% human serum, at least for the first 24 h, a time equivalent to three parasite erythrocytic life-cycles. Lipid transfer from HDL to the intra-erythrocytic parasites was demonstrated by uptake and exchange of fluorescent NBD-phosphatidylcholine (NBD-PC) loaded HDL at different temperatures. Kinetic experiments with [3H]-oleyl-PC-loaded HDL demonstrated a unidirectional transfer of lipids from radiolabelled HDL to the parasite; partial conversion of PC to phosphatidylethanolamine (PE) was also observed. In the semi-defined medium, the HDL fraction appeared to be the major source of lipids for the growth of B divergens in human erythrocytes.

Acetates↗

Heat shock response of Babesia divergens and identification of the hsp70 as an immunodominant early antigen during ox, gerbil and human babesiosis.

Using antisera (alpha-R and alpha-C7Ag) directed against the conserved Gly-Gly-Met-Pro-epitope of the hsp70 family, a single antigen was identified in the human Babesia divergens Rouen 1987 isolate by Western immunoblotting and immunoprecipitation experiments. This B divergens hsp70 is highly conserved as shown by the analysis of five other geographical B divergens isolates from different hosts (human and bovine). Indirect immunofluorescence assay performed on the asexual intraerythrocytic stages showed that the hsp70 is mainly cytoplasmic and stage-independent. Heat-shock experiments, with 20 min incubation at 40 degrees C followed by a 10 to 50 min shift to 37 degrees C in the presence of [35S]-methionine, led to an increase of two hsp of 85 and 70 kDa while protein synthesis in general decreased within 10 min. Immunoprecipitations of [35S]-methionine radiolabelled proteins with human, ox and gerbil antisera raised against various B divergens isolates, showed the presence of a B divergens 70 kDa protein which was demonstrated to be a hsp70 by coupling immunoblotting assays with alpha-C7Ag serum on the same immunoprecipitated material. During human babesiosis, the B divergens hsp70 appears as an early antigen during the acute phase. These results are in agreement with the use of the B divergens hsp70 as an essential valence antigen in an anti-babesiosis vaccine.

Amino Acid Sequence↗

Analysis of immune responses of different hosts to Babesia divergens isolates from different geographic areas and capacity of culture-derived exoantigens to induce efficient cross-protection.

The immunoprecipitation of [35S]methionine-radiolabelled antigens from different Babesia divergens isolates by using bovine, gerbil, and human immune sera has shown that many B. divergens proteins contain epitopes shared between isolates. The cross-protective capacity of culture-derived soluble immunogens from the B. divergens Rouen 1987 isolate was tested against different B. divergens isolates. Results showed complete protection against the 7107b French isolate and substantial protection against the Weybridge 8843 English isolate (80% protection) and the Munich 87 German isolate (60% protection). In order to explain these vaccination results and to assess both the common and variable antigenicity of B. divergens, the antigenic patterns of the challenge isolates (Rouen 1987, 7107b, Weybridge 8843, and Munich 87) were compared by immunoprecipitation, using gerbil antisera raised against the Rouen 1987 vaccine isolate. Differences in the antigenic patterns and in the cross-protection of gerbils in these heterologous challenges were examined by studying the virulence and the antigenic status of each isolate.

Animals↗

In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection.

In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates.

Acquired Immunodeficiency Syndrome↗

The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells.

mAb 60.3 and IB4 to CD18, the common beta-subunit of the human leukocytic cell adhesion molecule family, efficiently inhibit syncytium formation induced by the interaction of HIV type 1 (HIV-1)-infected monocytoid cells and CD4+ T cells. The antibodies also interfere with cellfree HIV-1 infection of U-937 clone 16 cells. Virus-induced aggregation of these cells and the subsequent syncytia formation leading to massive cell death are efficiently blocked, and the number of infected cells remains at a very low level, 2 to 5%, for the entire culture period. However, anti-CD18 mAb do not inhibit binding of the viral envelope glycoprotein gp120 to the cell surface receptor CD4. The results indicate participation of CD18, or of the protein complex CD11a-c/CD18, in addition to CD4, in the infection and cytopathic effect of HIV-1. They also suggest that intercellular adhesion contributes to virus transmission from cell to cell and may be an important mechanism for virus spreading.

Antibodies, Monoclonal↗

[Steroid therapy in subarachnoid hemorrhage].

Increase in intracranial pressure due to brain oedema is one of the most frequent complications of subarachnoid hemorrhage (SAH), apart from vasospasm and hydrocephalus. Up to now the administration of corticosteroids at various dosages has been the standard therapy for brain oedema. With this retrospective study we tried to answer the question whether the administration of dexamethasone at high dosage in patients with SAH bears an increased risk of medical complications such as infections, gastrointestinal bleeding and diabetes mellitus. 171 consecutive patients of our intensive care unit, 51 men and 120 women (average age 52.4 +/- 13.6 years) were included in the study. 107 patients received dexamethasone in high doses according to Gobiet's scheme. 64 patients who were not given any steroids formed the control group. Almost the same frequency of gastrointestinal bleeding was registered in the steroid group (2.8%) and in the control group (3.1%). No increase in diabetic problems was found in the steroid group, either. The steroid group showed an increase in infections (38.3% compared with 28.1% in the control group; p less than 0.001). The increase, however, was entirely due to the more frequent occurrence of urinary tract infections (14.0% vs. 4.7%). Dexamethasone therapy at high dosage bears no increased risk of medical problems in patients with SAH, except for a greater number of urinary tract infections. However, stomach ulcer prophylaxis and monitoring of blood sugar levels and electrolytes are deemed necessary.

Adolescent↗

HIV-1 infection of normal human macrophage cultures: implication for silent infection.

We have investigated the replicative capacity of 14 primary HIV-1 isolates in cultures of normal blood macrophages and PHA-stimulated peripheral blood mononuclear cells (PBMC). All viruses could infect normal macrophages as demonstrated by either reverse transcriptase (RT) activity, p24 antigen assay, or cocultivation with PBMC. One month after infection of macrophages virus could no longer be detected in the culture medium. The cells remained in this nonproductive state for another month. Virus could, however, be recovered by cocultivation with PHA-stimulated PBMC. Such macrophage-passaged virus induced pronounced cell killing with fragmentation and pyknosis and often replicated poorly in PBMC, in contrast to the original isolate. The results indicate that all primary HIV-1 isolates contain virus variants that can infect cells of the monocyte/macrophage lineage. Persistently infected, seemingly nonproducing cells, may serve as infectious reservoirs in the infected individual and spread infection to other susceptible cells over a long period of time. Moreover, the pronounced killing of PBMC by the macrophage-harbored virus may contribute to the deterioration of the immune system.

Cell Survival↗

Characterization of the in vitro maturation of monocytes and the susceptibility to HIV infection.

The in vitro maturation of peripheral blood monocytes to macrophages can be followed morphologically, and by measurement of cell surface antigens (CD4, HLA-DR, and FcR III) and lysozyme production. We used these markers to correlate monocyte maturation with susceptibility to human immunodeficiency virus (HIV) infection. Maturation of peripheral blood monocytes is associated with a decrease in membrane CD4, while HLA-DR and FcR III expression increase along with lysozyme secretion. Cells at all stages of maturation were susceptible to HIV infection, even mature macrophages without CD4 detectably by immunofluorescent staining. Maximal replication was observed in 7-day-old cells.

Antibodies, Monoclonal↗

Replicative capacity of HIV-2, like HIV-1, correlates with severity of immunodeficiency.

We have obtained 15 HIV-2 isolates from the peripheral blood mononuclear cells (PBMCs) of 24 HIV-2-infected west African people. The frequency of virus isolation correlated with the severity of HIV-2 infection; only three isolates were obtained from 11 asymptomatic individuals, whereas virus was isolated from nearly all (12 of 13) individuals with symptoms. The HIV-2 isolates showed distinct replicative and cytopathic characteristics and, similarly to HIV-1 isolates, could be divided into two major groups: rapid/high and slow/low. Rapid/high isolates, i.e. isolates with the ability to replicate in tumour cell lines, were obtained from individuals with symptomatic HIV-2 infection and CD4+ lymphocyte counts less than 360/microliters blood; these isolates induced syncytia in PBMC cultures. HIV-2 isolates unable to replicate continuously in tumour cell lines (slow/low isolates) induced small syncytia, cell death, or no cytopathic effect at all. All HIV-2 isolates obtained from asymptomatic individuals showed a slow/low replication pattern.

Acquired Immunodeficiency Syndrome↗

Transcranial Doppler monitoring during percutaneous transluminal aortic valvuloplasty.

Cerebral blood flow was studied in 12 elderly patients with severe calcific aortic stenosis by means of transcranial Doppler sonography (TCD) during percutaneous transluminal aortic valvuloplasty (PTAV). In 8 of these 12 patients duplex sonography revealed a stenosis of the internal carotid artery (ICA) exceeding 50%. Frequency spectra of 10 patients showed a satisfactory quality and were analyzed. In 7 subjects balloon inflation was well tolerated and systolic blood pressure did not drop below 75 mmHg. In these patients, whether they had a stenosis of the ICA or not, blood flow velocity in the middle cerebral artery (MCA) did not decrease to a critical level. The authors defined "critical" as a reduction of mean blood flow velocity in the MCA exceeding 50% or a decrease below 35 cm/sec. Three patients showed a rapid decrease of systolic aortic pressure below 75 mmHg. In these subjects mean blood flow velocity in the MCA dropped to levels below 35 cm/sec. Deflation and retraction of the balloon resulted in a rapid increase of systemic blood pressure and flow velocity in the MCA. This report demonstrates TCD to be a useful monitoring method of determining residual perfusion in patients with aortic stenosis during PTAV.

Aged↗

Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years.

The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity.

Adult↗

["Diabetic rosettes": a cellular immunity marker in subjects at risk for type I diabetes].

The authors have previously described a marker of cell-mediated, called "diabetic rosettes", revealed by the increased binding of CD3 CD4 lymphocytes from type I diabetic patients to beta-cell membrane antigens, as compared to lymphocytes from control subjects. In the present study, they have detected such "diabetic rosettes" in some subjects at risk for type I diabetes. The mean value of lymphocytes adhering to beta (RINm5F)-cells (beta-CL) was statistically higher in those subjects at risk than in control blood bank donors (p = 0.003). When a positive test was arbitrarily defined as a value of beta-CL higher than the 95th percentile of controls, 20 p. cent of the subjects at risk were classified as beta-CL+. No difference was observed between two subgroups of subjects at risk: first degree relatives of type I diabetic patients, and non-diabetic subjects with transient hyperglycaemia. "Diabetic rosettes" were associated with HLA DR 3/4 heterozygosity (p less than 0.04) and with a "low" acute insulin release to IV glucose (p = 0.05). They were not associated with islet-cell antibodies, insulin autoantibodies, or "activated" (HLA DR+) T-lymphocytes. The authors suggest that "diabetic rosettes" represent a marker of cellular immunity in some subjects at risk for type I diabetes.

Adolescent↗

Biological characterization of paired human immunodeficiency virus type 1 isolates from blood and cerebrospinal fluid.

Virus has been isolated from the blood and cerebrospinal fluid (CSF) of eight subjects with varying severity of human immunodeficiency virus type 1 (HIV-1) infection and from the frontal lobe of one patient with AIDS. The five patients with AIDS-related complex (ARC) and AIDS also showed neurological/psychiatric complications. With the exception of one isolate from the CSF of an asymptomatic carrier, all isolates replicated in peripheral blood mononuclear cells and monocytes after cell-free transmission. Isolates obtained from the blood of patients in late stages of HIV infection replicated in 3 (of 4) cases in H9 cells, whereas none of the blood isolates from patients in the early stages did so. The capacity of CSF isolates to replicate in H9 cells was low (only 2 of 12). Paired virus isolates from blood and CSF of the same patient could be distinguished by their replicative capacity in different cell lines, type of cytopathic effect, and protein profile as tested by radioimmunoprecipitation. The results indicate that variant viruses with distinct biological characteristics may be isolated from the blood and CSF of the same patient.

AIDS Dementia Complex↗

Class II MHC antigen induction on rat insulinoma (RINm5F) and colon carcinoma (TS) cells by co-culture with diabetic and normal xenogenic lymphocytes.

Two MHC Class II-negative rat epithelial cell lines (RINm5F beta-cells and TS colic cells) were co-cultured with xenogenic lymphocytes from Type I diabetic patients or from low-dose streptozotocin (SZ) diabetic mice. MHC Class II antigens (Ag) were easily induced on both cell lines in such co-culture conditions, representing an experimental approach to insulitis. Our data indicate that: (1) lymphocytes from diabetic patients or from SZ mice were more efficient than lymphocytes from healthy controls in inducing Class II Ag on RIN cells. Lymphocytes from patients with autoimmune thyroid diseases were also more efficient than control lymphocytes, indicating that the ability to induce Class II may be related to the activation of lymphocytes rather than being diabetes-specific. (2) Rat colon carcinoma cells (TS) were also induced to express high levels of Class II Ag upon co-culture with SZ or control mouse lymphocytes. (3) Class II+ RIN cells were observed after 24 h of co-culture; their number increased after 48 and 72 h. The number of class II+ RIN increased proportionally to the number of lymphocytes in the culture. (4) Induction of Class II Ag was obtained by cell-free supernatants of mouse lymphocytes/RIN co-cultures and was inhibited by cyclosporine A, suggesting that Class II induction in this model is mediated by lymphokines. (5) Depletion experiments indicate that both monocytes and lymphocytes play a role in this Class II induction.

Animals↗