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Biomedical subjects

C Schmitt

Publications and source records attributed to C Schmitt.

At least 19 recordsLinked to original sources
PubMed1995

[Radiofrequency ablation in permanent ectopic left atrial tachycardia].

HISTORY AND FINDINGS: A 35-year-old symptom-free woman was known since childhood to have an increased resting heart rate (130-150/min). In the ECG there was a negative P in leads I and aVL, with a shortened P-Q interval of 90 ms. Previous treatment with beta-receptor blockers and calcium antagonists had failed. Clinical examination and echocardiography, as well as levels of thyroid hormone were unremarkable. During electrophysiological studies the earliest atrial activity was localised by endocardial leads in the region of the distal coronary sinus and the arrhythmia could not be terminated by atrial over-stimulation. TREATMENT AND COURSE: After transseptal puncture the ablation catheter was introduced into the left atrium and, the exact site of the origin of the atrial tachycardia having been established, radiofrequency ablation of this point was successfully performed. Subsequently the patient was always found to be in stable sinus rhythm at around 80/min. CONCLUSION: To prevent tachycardia-induced cardiomyopathy, radiofrequency ablation can be indicated even in symptom-free patients with atrial tachycardia.

Adult↗
PubMed1995

Phosphorylation in halobacterial signal transduction.

Regulated phosphorylation of proteins has been shown to be a hallmark of signal transduction mechanisms in both Eubacteria and Eukarya. Here we demonstrate that phosphorylation and dephosphorylation are also the underlying mechanism of chemo- and phototactic signal transduction in Archaea, the third branch of the living world. Cloning and sequencing of the region upstream of the cheA gene, known to be required for chemo- and phototaxis in Halobacterium salinarium, has identified cheY and cheB analogs which appear to form part of an operon which also includes cheA and the following open reading frame of 585 nucleotides. The CheY and CheB proteins have 31.3 and 37.5% sequence identity compared with the known signal transduction proteins CheY and CheB from Escherichia coli, respectively. The biochemical activities of both CheA and CheY were investigated following their expression in E.coli, isolation and renaturation. Wild-type CheA could be phosphorylated in a time-dependent manner in the presence of [gamma-32P]ATP and Mg2+, whereas the mutant CheA(H44Q) remained unlabeled. Phosphorylated CheA was dephosphorylated rapidly by the addition of wild-type CheY. The mutant CheY(D53A) had no effect on phosphorylated CheA. The mechanism of chemo- and phototactic signal transduction in the Archaeon H.salinarium, therefore, is similar to the two-component signaling system known from chemotaxis in the eubacterium E.coli.

Amino Acid Sequence↗
PubMed1995

CD34-positive early human thymocytes: T cell receptor and cytokine receptor gene expression.

CD34, a stem cell marker, has been shown to be expressed on human CD3-CD4-CD8- (triple-negative; TN) thymocytes. Phenotypic and functional analyses suggest the following differentiation sequence: CD34+1-3-4-8(-)--> CD34+1+3-4 +/- 8(-)-->CD34-1+3-4+8(+/-)-->CD34-1++3-4+8+. In this report, we examined cytokine receptor gene expression on these subsets by reverse transcription-polymerase chain reaction analysis (RT-PCR). We were able to detect interleukin-7 receptor (IL-7R), c-kit and IL-2R gamma in all CD34+ thymocyte subsets, consistent with previous functional studies. We found IL-1R, granulocyte/macrophage colony-stimulating factor receptor-alpha and IL-4R transcripts in CD3- and CD34+ subsets. Secondly, we investigated T cell receptor (TCR)-delta and -beta gene rearrangement and transcription in CD34+ thymocytes. Our results show that a full-length TCR-delta transcript and the recombination activating genes RAG-1 and RAG-2 mRNA were already expressed in the CD34+1- subset. Mature V beta-containing TCR transcripts were also detected in the CD34+1+ subset, but not in the CD1- fraction. Furthermore, PCR analysis of D-J beta gene rearrangements showed that > or = 70% of CD34+1- cells are in a TCR beta germ-line configuration, although D-J beta recombination had already started in this population.

Antigens, CD34↗
PubMed1995

Association of intermediate uveitis with HLA-A28: definition of a new systemic syndrome?

BACKGROUND: Endogenous posterior uveitis (PU) can be associated with systemic diseases, and certain forms have strong association with HLA antigens. Much less is known regarding intermediate uveitis (IU). The purpose of this study was to determine whether IU is associated with the HLA system and whether it can be associated with systemic symptoms. METHODS: In 179 consecutive patients consulting for uveitis, a detailed history was obtained and a physical examination performed. HLA typing for 71 HLA-A, B, DR and DQ antigens, laboratory tests, and radiography of the chest, sinuses, and sacroiliac joints were systematically performed. RESULTS: Thirty-two patients (18%) had IU; 51 (28.5%) had PU and constituted our internal control group. Nine of the patients with IU (28%) had the HLA-A28 antigen, compared with 8.1% of a healthy control population and 8.6% of the patients with PU (P < 0.001). An associated disease was found in four patients with IU (12.5%) (none was HLA-A28) and in 45% of the patients with PU (P < 0.01). Some 67% of HLA-A28 patients with IU had arthralgias affecting the knee(s), compared with 17% of non-HLA-A28 patients and 18% of patients with PU (P < 0.05 and P < 0.01 respectively); 55% had gonalgias and hypocomplementemia compared with 9% and 2% respectively (P < 0.01 and P < 0.001). CONCLUSIONS: IU is significantly associated with HLA-A28; patients having this antigen may represent a subset of the disease characterized by an increased prevalence of arthralgias and hypocomplementemia.

Adolescent↗
PubMed1995

[Favorable outcome of orbital nasal sinus mucormycosis complicating the induction treatment of acute lymphoblastic leukemia].

BACKGROUND: Most cases of mucormycosis occur in immunosuppressed children. Intracranial extension is lethal and must be prevented with early specific treatment. CASE REPORT: A 42 month-old boy was admitted suffering from acute lymphoblastic leukemia. Edema of the left eyelid developed on the sixth day of induction chemotherapy. Mucormycosis was suspected because of gradual extension of infection to nasal ala and periorbital area with fever, edema of nasal turbinates and nasal black secretions. Chemotherapy was discontinued and the patient was given intravenous amphotericin B (1.0 mg/kg/day) and heparin associated with G.CSF. Improvement was only temporary and scan examination performed on day 17 showed involvement of the orbit, eye and wall of the maxillary sinus; cultures of secretions were positive for staphylococcus and Absidia corymbifera. Remission of leukemia was obtained a few days later permitting surgical resection of involved tissues on day 30. A relapse of mucormycosis was observed six weeks later despite prolonged administration of amphotericin B requiring extended resection of necrotic areas and replacement of amphotericin B by its liposomal form (Ambisome). Bone marrow relapse of leukemia required further chemotherapy. The patient is in good condition 30 months after the initial symptoms. CONCLUSION: Our patient seems to be the first with prolonged remission of facial mucormycosis and acute leukemia despite relapse of both diseases. This favorable outcome could be due to the use of Ambisome.

Amphotericin B↗
PubMed1995

In vitro infection of peripheral blood mononuclear cells by hepatitis C virus.

To study the in vitro susceptibility of peripheral blood mononuclear cells (PBMC) to hepatitis C virus (HCV), we incubated cells from healthy donors with HCV-positive sera. Using RT-PCR and in situ hybridization, the genomic viral RNA was detected in PBMC and in their supernatants until 25 days post-incubation. The PBMC of the different donors were not all permissive to HCV, but results were more constantly positive when cells from four donors were pooled. Quantification of the genomic viral RNA by the branched-DNA assay showed a decrease in the HCV RNA concentration during the first week of culture followed by a peak during the second or third week, and also an increase in the total amount of viral RNA in the inoculated cells. Although HCV RNA could be detected in the supernatants by RT-PCR, the concentration was very low. Using a sense-specific RT-PCR method, the HCV negative-strand was also detected in the cells but not in the supernatants. In two experiments PBMC were successfully infected using HCV-positive culture supernatants, therefore suggesting that infectious particles can be produced in this system. Our findings demonstrate that PBMC are permissive for HCV replication in vitro but the replication level is very low. The HCV RNA concentration measured in PBMC of 10 chronically infected patients was not significantly higher than the maximal concentration obtained in PBMC infected in vitro.

Base Sequence↗
PubMed1995

CD34-positive early stages of human T-cell differentiation.

Thymus, the main organ for T lymphopoiesis, requires a permanent influx of progenitors from bone marrow (BM) or fetal liver. An essential question relating to early T-cell development is the identification of the progenitor population which actually homes to the thymus. Recent findings have shown that human multipotent progenitor/stem cells expressing CD34 have the capacity to differentiate into T cells when introduced into a thymic environment. More mature CD34+ bone marrow cells coexpressing CD7 and having a poor myeloid differentiation capacity can also efficiently differentiate into T cells in vitro. These lymphoid committed precursors might be the true thymic repopulating cells. In the thymus, cells with a similar CD34+7+ phenotype include the most primitive thymocyte precursors. CD34+ thymocytes have no myeloid differentiation potential, but may include precursors for natural killer (NK) cells. Interleukin-7 (IL7) is a potent in vitro growth factor for CD34+ thymocytes. Whereas current data do not support a crucial role for IL2, patients with IL2 receptor gamma chain (IL2R gamma) deficiency lack T- and NK cells. The recent demonstration that IL2R gamma is part of the receptor for IL7 strongly suggests that this cytokine plays an essential role in in vivo T lymphocyte and NK development.

Animals↗
PubMed1995

Porphyria cutanea tarda and hepatitis C viral infection. A clinical and virologic study.

BACKGROUND AND DESIGN: The role of hepatitis C virus (HCV) infection in porphyria cutanea tarda (PCT) is probable since the global HCV antibody prevalence among patients with PCT is about 70%. The purpose of this study was to evaluate the virologic characteristics in 12 patients with sporadic PCT and in one patient with familial PCT. Anti-HCV antibodies were detected by enzyme-linked immunosorbent assay and confirmed by recombinant immunoblot assay. Hepatitis B virus and antihuman immunodeficiency virus markers were also determined. The polymerase chain reaction was performed to detect the following: (1) both positive and negative HCV RNA strands, (2) HCV RNA titer, and (3) HCV RNA genotype. RESULTS: Seven of the 12 patients with sporadic PCT were HCV positive, and the patient with familial PCT was HCV negative. The age at onset of PCT was significantly lower in HCV-positive patients than in HCV-negative patients. The HCV RNA was detected in all patients who had HCV antibodies, and the replicative intermediate of HCV was detected in three of them. The positive RNA titer ranged from 1:10 to 1:10(6). Four patients were infected by HCV genotype I, two by genotype II, and one patient was coinfected by type I and type II. Three of the seven HCV-positive patients also had HBV antibodies, but HBV DNA was never detected. All patients were negative for the human immunodeficiency virus. CONCLUSIONS: The HCV infection rate was high (58%) in this series, and all HCV-infected patients had HCV RNA, reflecting an active replication of the virus. The young age at onset of PCT suggests that HCV is a major triggering factor of PCT. Nevertheless, the clinical changes of PCT were not related to the virologic findings, suggesting an indirect role of HCV.

Adult↗
PubMed1995

[Inflammatory myofibroblastic tumor of the lung with endobronchial, infiltrating, multifocal and recurrent form].

Pulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor, plasma cell granuloma) was reported most often as a single peripheral mass, successfully cured by surgery. A 14-year-old girl presented with a large left pulmonary mass involving and obliterating the main bronchus; there were angioinvasion and infiltration of mediastinum, hilar lymph nodes and pleura. Multiple, often tiny nodules were seen in the right lung. At microscopic examination, there were lymphocytic and plasmacytic infiltrates and borderline myofibroblastic proliferation with focal nuclear anaplasia. Smaller lesions were similar to organizing pneumonia. Disease was progressive in the remaining right lung after surgical resection and a two-month treatment with corticoids. The patient was then treated with chemotherapy. She was alive and well (twenty-month follow-up).

Adolescent↗
PubMed1994

Isolation and identification of two CD34+ cell subpopulations from normal human peripheral blood.

Circulating CD34+ progenitors were separated from normal human peripheral blood on the basis of size and density by counterflow centrifugal elutriation (CCE). The CD34+ cells, 0.15% of peripheral blood mononuclear cells, were heterogeneous with respect to their elutriation characteristics, mainly size and density. The least mature CD34+ cells, characterized by lack of CD38 antigen, were predominantly found in the small lymphoid cell fraction. In fractions containing larger and denser cells (large lymphocytes, monocytes, and granulocytes), CD38 was increasingly expressed on the CD34+ cells, as were lineage commitment markers CD10 (B lymphoid), CD33 (myeloid), CD13 (myelomonocytic) and CD71 (erythroid) antigens. The smaller and less dense CD34+ cells expressed CD34 antigen brightly while the larger and denser CD34+ cells expressed it dimly. The smaller and less dense CD34+ high cells failed to establish colony growth in short-term culture while the larger and denser CD34+low cells gave rise to high counts of colony forming units-granulocyte macrophage (CFU-GM). Physical separation on the basis of size and density by CCE differentiates between two main classes of steady-state CD34+ cells from normal human peripheral blood. The smaller and less dense CD34+high cells correspond to the earliest progenitors that express differentiation markers poorly but CD34 antigen brightly, do not give rise to short-term colony growth in vitro, and thus represent indirect evidence for pluripotent hematopoietic stem cells (PHSC). The larger and denser CD34+low cells are the more mature progenitor cells, already committed to myeloid, lymphoid or erythroid differentiation but only dimly expressing CD34 antigen, and these cells were responsible for short-term colony growth in vitro.

Adult↗
PubMed1994

Differential effect of transforming growth factor-beta 1 on the activation of human naive and memory CD4+ T lymphocytes.

Transforming growth factor-beta 1 (TGF-beta 1) can have stimulatory or inhibitory effects on cell growth. For several cell types, the effect of TGF-beta 1 was found to correlate with the differentiation stage of the cells and the presence of other cytokines. We have studied here the influence of TGF-beta 1 on CD4+ T cell activation in relation to the differentiation stage of the cells by evaluating the effect of TGF-beta 1 on the proliferative responses of purified CD4+CD45RA+ (unprimed) and CD4+CD45RO+ (primed) lymphocytes. Under certain conditions, TGF-beta 1 exerted a co-stimulatory effect on peripheral blood CD4+CD45RA+ T cells whereas the outgrowth of CD4+CD45RO+ T cells was suppressed in any activation system tested. The enhancement of proliferative responses by TGF-beta 1 in TCR/CD3 or CD2 stimulated cultures of CD45RA+ cells involved up-regulation of CD25 expression and was dependent on the presence of exogenous IL-2 or CD28 mAbs; IL-7 driven proliferative responses were suppressed by TGF-beta 1. These observations were confirmed in experiments with purified cord blood (CB) CD4+ T cells inasmuch as addition of TGF-beta 1 caused a 2- to 7-fold increase in IL-2 driven proliferative responses of these cells. Finally we show that, in contrast to the effect of TGF-beta 1 during primary stimulation of CD CD4+ T cells, TGF-beta 1 suppressed T cell proliferation for approximately 40% in secondary cultures of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Significance of supraventricular tachyarrhythmias in patients with implanted pacing cardioverter defibrillators.

Eighty-six patients were treated with an implantable cardioverter defibrillator (ICD) because of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). In 27 patients an epicardial system was used, in 59 patients a transvenous system with a subcutaneous patch electrode was implanted. During a mean follow-up time of 17 +/- 9 months, inappropriate activations of the ICD due to supraventricular tachycardia were documented by Holter monitoring in 14 patients (16%). In 8 patients paroxysmal atrial fibrillation (AF), in 2 patients chronic AF, in 1 patient atrial flutter, and in 3 patients sinus tachycardia triggered antitachycardia pacing functions (12 patients) or internal defibrillation (2 patients). In 3 patients (5%) VT was induced by inappropriate antitachycardia pacing. In an additional 18 patients (21%) inappropriate activation of antitachycardia functions due to atrial tachyarrhythmias were suspected based on telemetry readouts or the patient's history. Inappropriate activation of ICD therapy triggered by intermittent supraventricular tachyarrhythmias is common. Further improvements of detection algorithms for supraventricular tachycardia are required in future device generations.

Amiodarone↗
PubMed1994

Ocular drug safety and HMG-CoA-reductase inhibitors.

150 patients suffering from primary hypercholesterolemia were divided into three different groups receiving (1) lovastatin, (2) simvastatin, or (3) fenofibrate as controls. The aim of the study was to detect possible drug-induced ocular side effects, especially in the lens. The study period was 2 years. Ophthalmological examination and Scheimpflug photography were performed at the beginning and every 6 months. Increases or decreases in the visual acuity were distributed very similarly in the three groups. Definite evidence of side effects was not found, nor was there evidence of deleterious effects on refraction. The intraocular pressure revealed intraindividual fluctuations without clinical significance. Many changes were observed in the lens, all were minimal, including those of the extreme lens periphery which had no effect on visual acuity. The present study shows the great value of Scheimpflug photography with densitometric image analyses because of its objectivity when compared with other methods. Our observations provide good evidence that lovastatin and simvastatin have no undesirable toxic effects on the lens and other ocular tissues, compared with fenofibrate.

Color Perception↗
PubMed1994

Differential effects of D-sotalol on endocardial and epicardial action potentials of human ventricular myocardium in dilated cardiomyopathy.

The frequency- and concentration-dependent electrophysiologic effects of D-sotalol (3 x 10(-5)-10(-3) M) were evaluated in human epicardial and endocardial left ventricular (LV) myocardium. Intracellular action potentials (AP) were obtained from explanted hearts of 5 patients with dilated cardiomyopathy in whom orthotopic heart transplantation was performed. The following parameters were recorded: AP amplitude (APA), resting membrane potential (RMP), AP duration at 95 and 50% repolarization (APD95, APD50), maximal upstroke velocity (Vmax), and effective refractory period (ERP) at cycle lengths (CL) of 0.5, 1 Hz, and 1.5 Hz. APD50, APD95, and ERP were significantly prolonged in endocardium at D-sotalol concentration > or = 10(-4) M at all CL. In epicardium, APD50, APD95, and ERP were significantly prolonged at lower D-sotalol concentrations (starting at 3 x 10(-5) M). In contrast to parameters in endocardium, APD50, APD95, and ERP were shortened in epicardial cells at D-sotalol concentrations > or = 3 x 10(-4) M at drive CL of 0.5 and 1 Hz with no effect on Vmax and APA. In endocardium, the prolongation of APD95 and ERP was less at a CL of 1.5 Hz compared with 0.5 Hz at a concentration of 10(-4) M. This frequency-dependent effect was not observed in epicardium. No effects were observed on RMP, APA, or Vmax. These data indicate a differential effect of D-sotalol in endo- and epicardial human ventricular myocardium, which may be an important mechanism of action of D-sotalol.

Action Potentials↗
PubMed1994

Initial management of recurrent vulvovaginal candidiasis with oral ketoconazole and topical clotrimazole.

In a randomized study, 151 women with a history of recurrent vulvovaginal candidiasis and suffering from an acute episode of candidal vaginitis were assigned to receive either oral ketoconazole, 400 mg daily for 14 days, or clotrimazole vaginal suppositories, 100 mg daily for 7 days. One week after completion of therapy, evaluation revealed a clinical cure or improvement in 86.4% of ketoconazole- and 81.7% of clotrimazole-treated patients (P > .5), with a mycologic response in 80.3% and 81.7%, respectively. In the absence of maintenance suppressive antimycotic therapy, further follow-up for two months revealed an extremely high rate of clinical and mycologic failure in both groups, reaching 52.5% after ketoconazole and 62.6% after clotrimazole (NS). Adverse effects were significantly more common with systemic ketoconazole than accompanying topical clotrimazole therapy. Although both forms of antifungal therapy were highly successful in inducing clinical and mycologic remission in patients with recurrent vulvovaginal candidiasis, this study emphasized the need for immediate initiation of maintenance therapy following an initial clinical improvement.

Acute Disease↗