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Biomedical subjects

C Schneider

Publications and source records attributed to C Schneider.

At least 145 records · Page 8Linked to original sources
PubMed2000

Cardiovascular autonomic function, autoantibodies, and esophageal motor activity in patients with systemic sclerosis and mixed connective tissue disease.

OBJECTIVE: To study cardiovascular autonomic nerve function and presence of autoantibodies in relation to esophageal motor activity in patients with systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). METHODS: Twenty-five patients with SSc (13 limited, 12 diffuse cutaneous disease; disease duration 1-19 yrs) and 6 patients with MCTD (disease duration 1-10 yrs) were studied. Cardiovascular autonomic function was assessed using 5 standard tests and autoantibody status determined. Esophageal motor activity and lower and upper esophageal sphincter pressures were recorded manometrically. RESULTS: Five patients with SSc had definite, 7 borderline, and 13 no autonomic dysfunction; 23 had antinuclear. 9 anti-Sc170, 4 anticentromere, and 1 U1snRNP antibodies. Contraction amplitudes in the smooth muscle as well as the striated muscle esophagus and lower esophageal sphincter pressures were significantly lower and autonomic dysfunction more frequent in patients with than in those without anti-Sc170 (6 of 9 vs 6 of 16 patients); upper esophageal sphincter pressures did not differ. All patients with MCTD had antinuclear antibodies, 5 had definite autonomic dysfunction; their lower esophageal sphincter pressures were significantly lower than in SSc patients without anti-Sc170 and anti-U1snRNP. CONCLUSION: Esophageal motor dysfunction may be associated with the presence of anti-Sc170 and anti-U1snRNP autoantibodies and prevail in patients with cardiovascular autonomic neuropathy.

Adult↗
PubMed2000

Pulsatile expansion therapy for orbital enlargement.

Experimental and clinical investigations have documented the modulatory role of the globe in the development of the orbit. In cases of absence or early loss of the globe, severe hypoplasia of the orbit and midface has been reported by several authors. Statical conformers and orbital osteotomies have been used to correct the resulting facial asymmetry. When replacing such conformers by increasingly larger ones, orbital structures are negatively influenced by the repeated trauma of surgical interventions. Simulating the modulatory role of the globe on orbital growth was the objective when developing a pulsatile device for orbital enlargement in cases of anophthalmia and microrbitism. The design, application and preliminary experience with a dynamic, pulsatile expanding system are presented.

Anophthalmos↗
PubMed2000

[Animal experiment study on pros and cons of laparoscopic interventions on the liver].

The safety of laparoscopic liver resections compared to open procedure was to be evaluated in an animal study. Besides it had to be examined, whether onco-surgical principles could be kept sufficiently. Therefore 8 one-year-old pigs underwent laparoscopic liver resections; in 2 pigs left-lateral segmental resections were performed, in 5 left-sided hemi-hepatectomies and in one right-sided hemihepatectomy. It became obvious that a control of the vessels around the v. cava inf., of the left branch of the portal vein and of the suprahepatic veins was not possible with sufficient safety. Extraction of the preparations was a further problem. According to these results laparoscopic hemihepatectomy cannot be recommended for clinical routine. Further indications for a laparoscopic operation like deroofing of liver cysts, wedge-resections or treatment of superficial liver injuries are to be accepted.

Animals↗
PubMed2000

[Ocular toxocariasis. Value of local immunodiagnosis].

Toxocara canis is a nematode that may be involved in human ocular toxocariasis. Specific immunotesting is of importance but may be negative as toxocara antigens may localize exclusively in vitreous humor. We report here the case of one patient with optic disc toxocariasis granuloma negative for toxocara canis immunodiagnostic on serum. Clinical diagnosis was confirmed by toxocara canis specific enzyme-linked immunosorbent assay (ELISA) on aqueous humor showing elevated titers of antibodies. Systemic steroids associated to specific treatment of toxocariasis were initiated. Follow-up displayed regression of uveitis but development of vitreous bands leading to posterior retinal detachment. Toxocara posterior granuloma is of poor visual prognosis. Moreover, diagnosis may be of late setting, as clinical features are often unrecognized and specific immunodiagnostic on serum negative. Specific immunotesting on aqueous humor is of particular importance to rule out severe clinical differential diagnosis such as retinoblastoma in children. Ultrasound biomicroscopy (UBM) seems to be specific and sensitive in patients with a presumed diagnosis of peripheral toxocariasis. Granuloma surgery appears to yield good clinical results and allows histological confirmation of the diagnosis.

Adult↗
PubMed2000

[Prospective multicenter study of laparoscopic colorectal surgery. Quality assurance during introduction of new methods].

During the course of development of laparoscopic surgery, the first successful procedures involving the colorectum were reported already in 1991 and 1992. This having demonstrated the principal feasibility of such operations, a study was initiated in German speaking countries in 1995, with the aim of investigating the efficacy and quality of laparoscopic surgery and involving the collection of all the interventions on the colorectum carried out in the departments participating. In an initial step, and when the first 500 patients had been treated, an indication spectrum was identified, which differed from the typical spectra of open colorectal surgery in showing a clear preponderance of benign diseases. In terms of the intra-operative and post-operative complications developing after laparoscopic procedures, however, no differences were to be seen vis-a-vis open surgery. In 167 of the first 500 recorded patients, an intervention for carcinoma was done in curative intent. On the basis of a detailed analysis, no trend towards a restriction of the scope of the procedures was to be seen in the laparoscopically treated patients. Furthermore, the number of dissected lymph nodes, the number of injuries to the tumor and the distal margins of clearance in the case of rectal resections were comparable with those seen in studies on open surgery. In the next step of the analysis, now based on larger numbers of patients, an evaluation of the sigmoid diverticulitis subgroup was carried out. A distinct selection of the uncomplicated forms of diverticulitis was found, the rate of intra-operative and post-operative complications remained satisfactory and comparable with the figures known for open procedures. The anastomosis was created almost exclusively either transanal with the stapler, or handsewn after exteriorization. In comparison with open surgery, the rate of anastomotic insufficiencies in the laparoscopic study was no higher than seen in open surgery. The last remaining, an as yet unanswered question is that of the long-term oncological results. Only in a few years time, when a mean follow-up period of more than 5 years has been achieved and the unselected data of all patients are available will it be possible to make a statement on the local recurrence rate as a sign of surgical quality, and on disease-free survival and 5-year survival rates. Only then we will be able to make a definitive assessment of the place of laparoscopic surgical in oncological interventions done in curative intent in a comparison with a historical group of open surgical patients. Until then, all laparoscopic procedures on the colorectum carried out in curative intent should be limited to prospective studies.

Colorectal Neoplasms↗
PubMed2000

Primary carcinoma of the fallopian tube. A report of 19 cases with literature review.

Primary carcinoma of the fallopian tube is the rarest cancer of the female genital tract with an incidence of 0.5% of all gynecologic tumors. Since the first report in 1847 about 1,500 cases have been published. Due to similarity of the clinical presentation the staging and therapeutic management have been adapted to that of ovarian cancer. We retrospectively evaluated all the 19 patients who had been diagnosed with primary carcinoma of the fallopian tube at the Department of Obstetrics and Gynecology of the University of Zurich between 1977 and 1998. All lesions were staged according to the rules of FIGO adopted in 1991. At the time of diagnosis the median age was 62 (46-87) years. Twelve (63%) women revealed FIGO stage III-IV, whereas four (21%) and three (16%) patients were diagnosed in stage I and stage II, respectively. Eight (42%) women were nullipara. Histology showed serous-papillary carcinoma, in ten (53%) cases. The 5-year survival rate was 22% for all FIGO stages and 80% for stage I. None of the patients with stage III and IV survived 5 years. Ovarian cancer and primary carcinoma of the fallopian tube are similar in many aspects. Both carcinomas have a similar age distribution, show an increase among nulliparous women, are often of serous papillary histology, have a poor prognosis with stage and residual tumor size as important prognostic factors, and respond initially well to platinum-based chemotherapy. Nevertheless, there appears to be a difference between the two diseases: primary carcinoma of the fallopian tube is more often diagnosed in an earlier stage. This many be due to lower abdominal pain resulting from tubal dilatation and to abnormal bloody-watery discharge.

Adult↗
PubMed1999

wt p53 dependent expression of a membrane-associated isoform of adenylate kinase.

Six novel p53-inducible transcripts were recently cloned from Val5, a murine cell line stably expressing a temperature-sensitive p53 allele. One of the isolated clones represented a novel isoform of cytosolic adenylate kinase (AK1), a highly conserved monomeric enzyme involved in cellular homeostasis of adenine nucleotides. The corresponding protein, which we named AK1beta, was specifically induced upon activation of wt p53 in Val5 cells. The AK1beta protein differs from cytoplasmic AK1 by having 18 extra amino acids at the N-terminus. The extra residues in AK1beta provide a consensus signal for N-terminal myristoylation; as expected, AK1beta was shown to localize to the plasma membrane. The human AK1 gene contains several consensus p53 binding sites and we report that p53-dependent induction of the alternative AK1beta transcript also occurs in human cells. By using antisense ablation experiments in Val5 fibroblasts we show that AK1beta plays a relevant role in the establishment of reversible cell-cycle arrest as induced by p53 in these cells. These findings suggest that within a p53-dependent genetic program, a specific isoform of adenylate kinase has a previously undescribed growth-regulatory function, which might not necessarily require its best characterized biochemical activity.

3' Untranslated Regions↗
PubMed1999

Gas6-mediated survival in NIH3T3 cells activates stress signalling cascade and is independent of Ras.

Gas6 is a growth factor membrane of the vitamin K-dependent family of proteins which is preferentially expressed in quiescent cells. Gas6 was identified as the ligand for Axl tyrosine kinase receptor family. Consistent with this, Gas6 was previously reported to induce cell cycle re-entry of serum-starved NIH3T3 cells and to prevent cell death after complete growth factor withdrawal, the survival effect being uncoupled from Gas6-induced mitogenesis. We have previously demonstrated that both Gas6 mitogenic and survival effects are mediated by Src and the phosphatidylinositol3-OH kinase (PI3K). Here we report that Ras is required for Gas6 mitogenesis but is dispensable for its survival effect. Gas6-induced survival requires the activity of the small GTPases of the Rho family, Rac and Rho, together with the downstream kinase Pak. Overexpression of the respective dominant negative constructs abrogates Gas6-mediated survival functions. Addition of Gas6 to serum starved cells results in the activation of AKT/PKB and in the phosphorylation of the Bcl-2 family member, Bad. By ectopic expression of a catalytically inactive form of AKT/PKB, we demonstrate that AKT/PKB is necessary for Gas6-mediated survival functions. We further show evidence that Gas6 stimulation of serum starved NIH3T3 cells results in a transient ERK, JNK/SAPK and p38 MAPK activation. Blocking ERK activation did not influence Gas6-induced survival, suggesting that such pathway is not involved in Gas6 protection from cell death. On the contrary we found that the late constitutive increase of p38 MAPK activity associated with cell death was downregulated in Gas6-treated NIH3T3 cells thus suggesting that Gas6 might promote survival by interfering with this pathway. Taken together the evidence here provided identity elements involved in Gas6 signalling more specifically elucidating the pathway responsible for Gas6-induced cell survival under conditions that do not allow cell proliferation.

3T3 Cells↗
PubMed1999

Involvement of the 92-kDa gelatinase (matrix metalloproteinase-9) in the ceramide-mediated inhibition of human keratinocyte growth.

Triggering the ceramide pathway by exogenous treatment with neutral sphingomyelinase (Smase) inhibited human keratinocyte growth rate, while having no influence on cell apoptosis. Increasing the ceramide content of keratinocytes with Smase (100 U/ml) or C6-ceramide (1 microM) enhanced matrix metalloproteinase (MMP)-9 production. On the contrary, levels of MMP-2 secretion were unchanged. The inhibition of keratinocyte growth rate induced by ceramide could be annihilated by a peptide hydroxamate MMP inhibitor or an MMP-9 blocking antibody. In addition, inhibiting MMP-9 activity in control keratinocyte culture was found to stimulate keratinocyte proliferation. These data suggest a pivotal function of MMP-9 in the control of keratinocyte growth.

Antibodies↗
PubMed1999

Identification and characterization of a new member of the gas3/PMP22 gene family in C. elegans.

The Gas3/PMP22 protein family is characterized by tetraspan transmembrane proteins. The gas3/PMP22 gene is highly expressed in Schwann cells of the peripheral nervous system, and different alterations of this gene are associated with hereditary demyelinating neuropathies, such as the Charcot-Marie-Tooth type 1A, the Dejerine-Sottas syndrome and the Hereditary Liability to Pressure Palsies (HNPP).Here, we report on the identification of at least one member of the Gas3/PMP22 family in the nematode C. elegans (C01C10.1b). C01C10.1b shares 36% of identical amino acids with the human Gas3/PMP22 and is characterized by four hydrophobic putative transmembrane domains. It lacks the typical N-linked glycosylation consensus in the first extracellular loop. C01C10.1b is transcribed as an operon downstream to the gene C01C10.1a, which encodes for a putative tetraspan protein with less conserved homology with the Gas3/PMP22 family. Interestingly, C01C10.1a contains three N-glycosylation sites at the C-terminus. Both genes are expressed in different nematode developmental stages and in the adults. The characterization of one member of the gas3/PMP22 family in C. elegans gives the opportunity to use this model organism to investigate the role of gas3/PMP22 in the regulation of cell proliferation and differentiation and its relation to the hereditary neurodegenerative diseases in humans.

Amino Acid Sequence↗
PubMed1999

Identification of both shared and distinct proteins in the major and minor spliceosomes.

In metazoans, two distinct spliceosomes catalyzing pre-messenger RNA splicing have been identified. Here, the human U11/U12 small nuclear ribonucleoprotein (snRNP), a subunit of the minor (U12-dependent) spliceosome, was isolated. Twenty U11/U12 proteins were identified, including subsets unique to the minor spliceosome or common to both spliceosomes. Common proteins include four U2 snRNP polypeptides that constitute the essential splicing factor SF3b. A 35-kilodalton U11-associated protein homologous to the U1 snRNP 70K protein was also identified. These data provide fundamental information about proteins of the minor spliceosome and shed light on its evolutionary relationship to the major spliceosome.

Amino Acid Sequence↗
PubMed1999

Association of acetylcholine receptor alpha-subunit gene expression in mixed thymoma with myasthenia gravis.

OBJECTIVE: To investigate the association of MG with the transcription of muscular or neuronal acetylcholine receptor (AChR) subunit genes in thymomas. BACKGROUND: Many steps in the pathogenesis of MG have been elucidated but, with rare exceptions, its etiology is unknown. In patients with MG with thymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmatic why MG develops in some patients but not in others. METHODS: Reverse transcriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies were carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between thymoma subtypes. RESULTS: Considering all thymomas (n = 35), no correlation was found between MG status and AChR gene expression as detected by RT-PCR. However, when histologically defined thymoma subtypes were studied separately, transcription of the muscular AChR P3A- alpha-subunit gene was significantly associated (alpha < 0.01) with the occurrence of MG in mixed thymomas (n = 17), but not in thymomas of the cortical type. For the other muscular AChR subunits (P3A+ alpha isoform, beta, gamma, delta, and epsilon) and the alpha2 and beta4 neuronal AChR subunits, no such correlation was detected. CONCLUSIONS: Expression of the P3A AChR alpha-subunit gene might be important for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically different thymoma subtypes.

Adult↗
PubMed1999

The human serum deprivation response gene (SDPR) maps to 2q32-q33 and codes for a phosphatidylserine-binding protein.

The serum deprivation response gene (SDPR, alias sdr) has been previously isolated for its high mRNA expression in serum-starved cells compared to contact-inhibited NIH3T3 cells; such regulation is not observed in single-oncogene transformed NIH3T3 cells after serum starvation. More recently Sdpr has been identified as a substrate of protein kinase C (PKC): this interaction determines the compartimentalization of PKC to caveolae, a plasma membrane invagination of which Sdpr is a major component. Lack of Sdpr-PKC interaction in transformed cells has been proposed to be involved in the alteration of PKC subcellular localization and substrate specificity. Here we report the cloning of the human SDPR homologue (HGMW-approved symbol SDPR) and its mapping to 2q32-q33 in the human genome. In analogy with the murine system, SDPR mRNA expression is increased when human fibroblasts are serum starved, it becomes down-regulated during synchronous cell-cycle reentry, but it is not induced in cells arrested by contact inhibition. Analysis of SDPR expression in human tissues reveals a near ubiquitous expression, with highest levels found in heart and lung. We show that human SDPR encodes PS-p68, a previously characterized phosphatidylserine-binding protein purified from human platelets. Accordingly, recombinant Sdpr is able to specifically bind phosphatidylserine in the absence of Ca2+. SDPR is homologous to two genes in the databank, one of which, srbc, is similarly regulated during growth arrest and encodes a phosphatidylserine-binding protein that is a substrate of PKC.

Amino Acid Sequence↗
PubMed1999

gas2 is a multifunctional gene involved in the regulation of apoptosis and chondrogenesis in the developing mouse limb.

The growth-arrest-specific 2 (gas2) gene was initially identified on account of its high level of expression in murine fibroblasts under growth arrest conditions, followed by downregulation upon reentry into the cell cycle (Schneider et al., Cell 54, 787-793, 1988). In this study, the expression patterns of the gas2 gene and the Gas2 peptide were established in the developing limbs of 11.5- to 14. 5-day mouse embryos. It was found that gas2 was expressed in the interdigital tissues, the chondrogenic regions, and the myogenic regions. Low-density limb culture and Brdu incorporation assays revealed that gas2 might play an important role in regulating chondrocyte proliferation and differentiation. Moreover, it might play a similar role during limb myogenesis. In addition to chondrogenesis and myogeneis, gas2 is involved in the execution of the apoptotic program in hindlimb interdigital tissues-by acting as a death substrate for caspase enzymes. TUNEL analysis demonstrated that the interdigital tissues underwent apoptosis between 13.5 and 15.5 days. Exactly at these time points, the C-terminal domain of the Gas2 peptide was cleaved as revealed by Western blot analysis. Moreover, pro-caspase-3 (an enzyme that can process Gas2) was cleaved into its active form in the interdigital tissues. The addition of zVAD-fmk, a caspase enzyme inhibitor, to 12.5-day-old hindlimbs maintained in organ culture revealed that the treatment inhibited interdigital cell death. This inhibition correlated with the absence of the Gas2 peptide and pro-caspase-3 cleavage. The data suggest that Gas2 might be involved in the execution of the apoptotic process.

Animals↗
PubMed1999

Protease inhibitor-containing regimens compared with nucleoside analogues alone in the suppression of persistent HIV-1 replication in lymphoid tissue.

OBJECTIVE: Lymphoid tissue provides a reservoir where HIV can persist. However, therapies incorporating a protease inhibitor can target this reservoir. This study was designed to investigate the relative long-term effects on lymph-node viral load and cellular architecture of regimens containing multiple nucleosides alone or in combination with protease inhibitors. METHODS: Axillary lymph-node biopsies from 12 patients with undetectable viraemia (viral load < 20 copies/ml: mean CD4 cells 525 x 10(6)/l) for a mean period of 25 months (range, 10-52 months) were investigated for the presence of HIV by in situ hybridization and coculture. Four patients were receiving multiple nucleoside analogues alone or in one case with a suboptimally dosed protease inhibitor (group I). Protease inhibitor was added to the regimen of seven patients at least 6 months prior to lymph-node biopsy (group II). Standard flow cytometry and virological data were obtained from peripheral blood every 3 months. RESULTS: By in situ hybridization, more productively infected CD4+ T cells were found in the lymph nodes of group I patients treated with nucleoside analogues alone. Very low numbers of productively infected lymph node cells were detected in the protease inhibitor-treated group II. No trapping of virions on the follicular dendritic cell (FDC) network was detectable in protease inhibitor-treated patients. In contrast, large deposits of FDC-bound virions were observed in three out of five patients from group I. Virus cultures from lymph node cells were positive in these three group I patients compared with only one out of seven patients from group II. Sequencing reverse transcriptase and protease genes from these isolates revealed typical mutations conferring resistance to the previously administered nucleoside analogue. A more preserved lymph node architecture and less signs of immunopathological change were also observed in protease inhibitor-treated patients. CONCLUSIONS: Undetectable plasma viraemia using the ultrasensitive PCR assay for prolonged periods of time does not always reflect complete HIV-1 suppression within the lymphoid compartment. Our results suggest that protease inhibitor-containing regimens target HIV reservoirs in lymphoid tissue more effectively and preserve or restore lymph node architecture.

Anti-HIV Agents↗
PubMed1999

Linkage of proximal myotonic myopathy to chromosome 3q.

We performed genetic linkage analysis in nine German proximal myotonic myopathy (PROMM) families using DNA-markers D3S1541 and D3S1589 from the region of the recently discovered gene locus of myotonic dystrophy type 2 (DM2) on chromosome 3q. Two-point analysis supplied an lod score of 5.9. We conclude that a gene causing PROMM is located on chromosome 3q. PROMM and DM2 may be allelic disorders or may be caused by closely linked genes.

Chromosome Mapping↗
PubMed1999

T-cell apoptosis in inflammatory neuromuscular disorders associated with human immunodeficiency virus infection.

BACKGROUND: Apoptosis is one of the major mechanisms of CD4+ T-cell depletion in human immunodeficiency virus (HIV) infection. T cells in human inflammatory myopathies in HIV-negative individuals rarely undergo apoptosis. Currently, there is no information available concerning the fate of T cells in HIV-associated myositis and polyneuropathies. OBJECTIVE: To investigate whether apoptosis occurs in inflammatory lesions of muscle and nerve biopsy specimens of untreated HIV-positive patients with neuromuscular disorders. METHODS: T-cell apoptosis was investigated in muscle and nerve specimens from 12 patients with HIV-associated polymyositis and 8 patients with HIV-associated inflammatory polyneuropathy. These were compared with specimens from 36 HIV-negative patients with other inflammatory myopathies and from 18 patients with inflammatory polyneuropathies. Apoptosis was assessed according to morphological criteria and with the use of in situ labeling methods. RESULTS: In none of the HIV-associated disorders did we observe a substantial proportion of apoptotic T cells as assessed by nuclear morphological findings and in situ labeling techniques. Fas expression was up-regulated only in a few inflammatory cells. Positive labeling for Fas ligand was not associated with increased apoptosis of surrounding T cells. Nuclei of degenerating muscle fibers and macrophages did not show morphological signs of apoptosis and were not labeled by the tailing reaction. CONCLUSIONS: Similar to their idiopathic counterparts, in HIV-related polymyositis and inflammatory neuropathy, T-cell inflammation is not cleared by apoptosis. The observations are consistent with the non-self-limited nature of endomysial or endoneural inflammation and suggest that in HIV-positive patients, the T-cell elimination is differentially regulated in the lymphoid organs as compared with neuromuscular tissues.

Apoptosis↗