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Biomedical subjects

A Schneider

Publications and source records attributed to A Schneider.

At least 19 recordsLinked to original sources
PubMed1992

Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene.

Proteolipid protein (PLP; M(r) 30,000) is a highly conserved major polytopic membrane protein in myelin but its cellular function remains obscure. Neurological mutant mice can often provide model systems for human genetic disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified first in the jimpy mouse and subsequently in patients with Pelizaeus-Merzbacher disease. The unexplained phenotype of these mutations includes degeneration and premature cell death of oligodendrocytes with associated hypomyelination. Here we show that a new mouse mutant rumpshaker is defined by the amino-acid substitution Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly, rumpshaker mice, although myelin-deficient, have normal longevity and a full complement of morphologically normal oligodendrocytes. Hypomyelination can thus be genetically separated from the PLP-dependent oligodendrocyte degeneration. We suggest that PLP has a vital function in glial cell development, distinct from its later role in myelin assembly, and that this dichotomy of action may explain the clinical spectrum of Pelizaeus-Merzbacher disease.

Amino Acid Sequence↗
PubMed1992

Surgical treatment for higher stage non-small cell lung cancer.

Locally advanced lung cancer (stage IIIa, IIIb) in which the primary tumor is proximal (T3) or has invaded adjacent structures (T3) or organs (T4) or in which mediastinal lymph nodes are involved (N2, N3) worsens the prognosis significantly. However, in stage IIIa (T3 or N2), when surgical treatment results in total removal of the primary tumor and involved lymph nodes, there still is a reasonable chance for ultimate cure. On the other hand, total excision can be very rarely performed in T4 or N3 tumors. Therefore, this group (stage IIIb) usually indicates unresectability. Disseminated lung cancer with distant metastasis (stage IV) is still considered to be incurable. Nevertheless, solitary metastatic sites (M1), especially brain, have been treated on occasion by resection of the primary tumor and removal of the solitary metastasis. This appears to improve median survival and does yield 5-year survival in selected patients. The results after surgical treatment in these patients with higher stage lung cancer reported over the last 10 years are reviewed.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization.

We have analyzed human papillomavirus (HPV) type 16 RNA expression in premalignant cervical lesions of different severity and in squamous cervical cancers by RNA-RNA in situ hybridization in order to find differences in the topographic distribution of viral RNA, which might correlate with the severity of disease. In the basal layer of low-grade squamous intraepithelial lesions (SIL) only weak transcription of viral early genes was observed. Signal intensity increased strongly in the more differentiated cells accompanied by high levels of HPV DNA replication. This pattern of viral gene expression, together with the onset of viral late transcription in the upper differentiated layer of the epithelium, most likely reflects the productive phase of viral infection. In contrast, in high-grade SIL viral transcription was comparatively strong in basal cells and evenly distributed throughout the undifferentiated epithelium. This difference of viral transcription in the basal layer of the respective lesions points to an altered regulation of viral gene expression which may be causally linked to the progression of precursor lesions. Evidence for disrupted expression of 3' early genes (E2, E4, and E5), analogous to the situation in HPV-DNA containing cervical carcinoma-derived cell lines, was not found in any of the HPV-16-positive premalignant lesions nor in the majority of cancers. The similarity of the viral transcription pattern of high-grade SIL and cancers suggests that additional host gene alterations are necessary for malignant progression.

Biopsy↗
PubMed1992

Human papillomavirus DNA in women without and with cytological abnormalities: results of a 5-year follow-up study.

To determine the prevalence of HPV 6, 11, 16, and 18 in a population without cytological or histological abnormalities, the cervical smears of women attending three clinics in Germany were screened over the past 5 years. The filter in situ hybridization method was used throughout. A total of 20,161 smears, taken from 11,667 women, were tested. When the results of only the first examination are considered, 8.8% (950/10,778) of women with normal cytology were positive for HPV DNA. If we divide the latter into age groups, 11% (852 HPV positive/7716) were below the age of 55 years and 3.2% (98 HPV positive/3062) were above this age. When the samples from patients who had undergone at least two examinations and remained cytologically negative during the 5-year period were examined (total, 2709 women), the HPV DNA positively increased to 34.7% (640/1862) for the sexually active age groups and to 9.0% (76/847) for those above 55 years of age. This study reveals that, although papillomaviral production is most pronounced in younger women, these infections are quite common in all age groups. During the period of investigation, 19 (0.65%) patients, who were diagnosed as cytologically negative at the first examination, progressed to carcinoma in situ or invasive carcinoma. Of these, 63.2% revealed a detectable HPV infection during the study period. The progression of HPV-positive women from normal cytology to CIN or cancer occurred at an annual frequency of 0.082%. With an infected lifespan of 45 years assumed, this results in a lifetime risk of 3.7%.

Adolescent↗
PubMed1992

[Hypogangliosis of the sigmoid colon: possibilities of sonographic diagnosis].

This case report concerns a 53-year old woman suffering from recurrent spastic pain and a painful "resistance" in the left lower bowel for the last 30 years. Earlier clinical investigations including endoscopy and laparoscopy did not yield any results. In a recent investigation, only sonography showed wall thickening and an echo-poor wall pattern of the sigmoid colon indicating this to be the site of painful resistance. Resection of the sigmoid colon was performed. Histologically a slight hypogangliosis of the colon and muscular hypertrophy were detected (as the only pathological signs). The patient was free from symptoms since operation. This case report proves that ultrasound may yield pointers (or confirm the diagnosis) in unclear abdominal diseases.

Female↗
PubMed1992

[The extraction particles from winter rapeseed with different glucosinolate fractions in swine with regard to the iodine supply. 3. Apparent digestibility of crude nutrients with special regard to the carbohydrate and nitrogen balance].

In two digestibility and N-balance experiments the following solvent extracted meals were examined in a grain (barley and wheat in equal parts) or in a starch diet with four female pigs/group fitted with urethra catheters during the 5 days sampling period: 48% soyabean meal (SBM) (1), 24% conventional rapeseed meal (RSM) (2), 24 (3) or 48% (4) RSM from a newly bred low glucosinolate variety, groups 1 to 4 with grain, 48% low glucosinolate RSM (5) or 48% SBM (6) both with starch. In numeric order of the groups 88, 85, 86, 84, 79 and 89% N were digested. Pigs responded to the additional faecal N excretion from RSM diets by a lower urinary N excretion and thus they reached the N-balance of the animals fed on SBM. In numeric order of the groups 86, 79, 80, 73, 73 and 92% of the organic matter of the solvent extracted meals were digested. In comparison with SBM even 48% RSM in the feed significantly lowered the digestibility of organic matter. Using detergents the additional faecal organic matter excretion of RSM versus SBM could quantified as two third lignin. In the case of 24% RSM in the diet--i.e. 15% of the carbohydrates given--the carbohydrate digestibility is estimated with a high error, that an energetic feed value should not calculated. Investigating 48% SBM or RSM respectively in a grain diet the net energy content was 9.8 MJ (666 Energetic Feed Units, EFU pig) or 8.3 MJ (569 EFU pig)/kg dry matter (DM). Based on the starch diet, however, little relevant for estimation of normal pig diets, there were evaluated 10.6 MJ (720 EFU pig) for SBM and 8.3 MJ (567 EFU pig) net energy/kg DM for RSM.

Animal Feed↗
PubMed1992

Beta-2-microglobulin-derived amyloidosis: onset, distribution and clinical features in 13 hemodialysed patients.

Postmortem examinations were carried out in 13 patients (6 males, 7 females, age 58 +/- 9 years) who had been on regular hemodialysis treatment for 10-90 months using disposable regenerated cellulose membrane dialyzers. The prevalence of beta 2-microglobulin (beta 2m)-derived AB-amyloid deposits in different sites was determined. At autopsy, specimens were obtained from different joints, paravertebral tissue, intervertebral discs and from visceral organs. During life, routine laboratory parameters and radiographic studies had been carried out at 6-month intervals. Serum levels of beta 2m were elevated in all patients (57.5 +/- 13.4 mg/l). Synovial AB-amyloid deposits were shown in different joints of 4 patients, aged between 59 and 73 years, and dialysed for 10-90 months, respectively. All had been unremarkable by X-ray and asymptomatic. No amyloid could be detected in the intervertebral discs of 2 further patients suffering from destructive spondylarthropathy. In 11 of the 13 patients, extracellular beta 2m deposits were observed by immunohistochemistry in different tissues. The results document that (a) AB-amyloidosis may occur in elderly patients even when dialysed for less than 5 years; (b) most cases are completely asymptomatic; the appearance of symptoms must be dependent on additional factors, e.g., site of AB-amyloid deposition and intensity of inflammatory reaction, and (c) AB-amyloid is not the exclusive cause of destructive spondylarthropathy, as 2 typical cases were observed who were devoid of amyloid.

Amyloidosis↗
PubMed1992

Repeated evaluation of human papillomavirus 16 status in cervical swabs of young women with a history of normal Papanicolaou smears.

This study was designed to compare single-point prevalence estimates with a cumulative prevalence estimate of human papillomavirus (HPV) type 16 in cervical smears. The influence of the menstrual cycle and the long-term effect of HPV 16 positivity on the development of cervical intraepithelial neoplasia (CIN) were monitored. We examined 21 women (median age 23.6 years) every 5 weeks for 1 year. All women had a history of negative Papanicolaou smears for at least 5 years before enrollment. Cervical swabs were collected at each visit for Papanicolaou smears and HPV 16 detection by the polymerase chain reaction. Five years after completion of the last visit, self-reported information regarding cervical neoplasia was obtained. Human papillomavirus type 16 point-prevalence estimates per visit varied between 14.3-33.3%. The cumulative prevalence was 66.7%; 14 women were positive at least once and seven women were continuously negative for HPV 16. Detection of HPV 16 was significantly higher in the luteal phase. Repeated positivity for HPV 16 by Southern blot and polymerase chain reaction preceded and accompanied CIN in one patient, whereas in the remaining patients, positivity for HPV 16 by polymerase chain reaction alone was not associated with CIN during a 5-year follow-up. Single-point measurements of HPV 16 in cervical smears by polymerase chain reaction are of limited value for assessment of an individual's HPV status. This should be kept in mind when HPV testing for screening programs is considered.

Adolescent↗
PubMed1992

Natural history and epidemiological features of genital HPV infection.

The spectrum of genital HPV infections comprises clinical, subclinical, and latent disease in addition to HPV-associated neoplasia. The definition of subclinical and latent HPV infection is still incomplete and awaits clarification by highly sensitive HPV detection systems that preserve the morphology of the tissue. Genital HPVs infect the human body mainly by sexual transmission, but other pathways of HPV transmission may be possible as suggested by (a) high prevalences of antibody reactivity in children; (b) lack of association of HPV seropositivity with sexual activity; (c) presence of HPV DNA in oral cavity scrapings of children and adults; and (d) development of recurrent respiratory papillomatosis among children exposed to HPV 6 or 11 during birth. Successful infection depends on the infection site and the immunological state of the host: susceptibility to genital HPVs seems highest for the squamous epithelium of the lower genital tract. HPV DNA is also present in extragenital sites but this is rarely accompanied by clinical or subclinical lesions. The molecular basis for this specific tropism is unknown. The immune response in HPV-infected tissues is characterized by depletion of T helper/inducer cells or Langerhans cells and an impaired immunological function of natural killer cells or the infected keratinocyte. Epidemiological studies indicate that individuals with cell-mediated immunodeficiencies are at increased risk for genital HPV infections. Data about the biological course of genital HPV infections are just beginning to emerge. Regression or persistence of subclinical and latent genital HPV infections as analysed in longitudinal investigations show a constant come-and-go of HPV presence. In an infected individual, complete clearing of the virus seems rather exceptional. With respect to progression, the biological potential of cervical HPV infections is characterized by an increased risk for development of HPV-associated neoplasia, especially in lesions infected with high-risk HPV types (e.g., HPV 16 and 18). Demographic data of genital HPV infections are very variable due to differences in the HPV detection assays used and in the populations examined; the prevalence of subclinical and latent genital HPV infections appears to be at least three times higher compared with clinical HPV infections. This rate increases by a further 3-5-fold when patients are examined several times. Seroreactivity against genital HPV types may be due to an active infection or the result of contact with HPV earlier in life.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Dose-range finding study with the proton pump inhibitor pantoprazole in acute duodenal ulcer patients.

Pantoprazole is a newly developed benzimidazole derivative with strong inhibitory actions on gastric acid secretion by blocking H(+)-K(+)-ATPase. This randomized double-blind multicenter trial investigated the efficacy of 20 mg, 40 mg and 80 mg pantoprazole o.m. on ulcer healing and symptomatic relief in 219 out-patients with endoscopically assessed acute duodenal ulcer. After 2 weeks complete ulcer healing was achieved in 58%, 89% and 82% of the patients with 20 mg, 40 mg and 80 mg pantoprazole o.m., respectively. After 4 weeks, corresponding figures were 93%, 99% and 100%; the difference of the healing rates between the 20 mg and 40 mg groups at 2 weeks was statistically significant (p < 0.0001). A rapid pain relief was achieved in all treatment groups: 72% of the 20 mg group, 89% of the 40 mg group, and 84% of the 80 mg group were pain-free after 2 weeks. The difference between 20 mg and 40 mg was statistically significant (p < 0.05). Pantoprazole was well tolerated. Adverse events occurred in 13 patients; headache, skin alterations, and diarrhea were reported most frequently. Severity and frequency of adverse events did not reveal any dose-dependence. In conclusion, pantoprazole provides fast healing of acute duodenal ulcer as well as rapid improvement of ulcer symptoms. For further clinical trials in peptic ulcer disease a daily dose of pantoprazole 40 mg o.m. is recommended.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

[Lobar restricted nodular form of pulmonary alveolar proteinosis].

A case report of a 53-year-old man with lobar restricted pulmonary alveolar proteinosis is presented. The way from an accidental X-ray examination until the final histological diagnosis of the specimen taken at operation is followed. Typical diagnostic pitfalls are discussed.

Diagnosis, Differential↗
PubMed1992

An improved method for endothelial cell seeding on polytetrafluoroethylene small caliber vascular grafts.

The creation of nonthrombogenic synthetic surfaces is a major challenge in biomedical research. The feature that clearly distinguishes natural blood vessels from their artificial counterparts is the presence of endothelial cell lining that besides being nonthrombogenic is capable of repair and renewal. This study describes a method of coating vascular grafts with a uniform, naturally produced subendothelial extracellular matrix before implantation. This substrate provides a most suitable bilayer for endothelial cell adhesion, growth, and differentiation, as compared with grafts coated with fibronectin or basement membrane extracts. It contains both adhesive glycoproteins (fibronectin, laminin, collagen) and proteoglycans (heparan sulfate) as well as endothelial cell growth factors (basic fibroblast growth factor) that support adhesion and normal growth of suboptimal concentrations of endothelial cells. We suggest that the presence in extracellular matrix of both adhesive macromolecules and potent endothelial cell-growth promoting factors will make the extracellular matrix a promising substrate for vascular grafts.

Animals↗
PubMed1991

Compartmentalization of cholesterol metabolism and cellular growth in cultured intestinal crypt cells.

Growth of rat intestinal crypt derived cells IEC-6 ceased when the key enzyme of cholesterol synthesis, hydroxymethylglutaryl-CoA reductase, was blocked by the competitive inhibitor mevinolin. This effect was reversed by the addition of mevalonolactone. LDL suppressed reductase activity as well as cholesterol synthesis from [14C]octanoate and stimulated acyl-CoA cholesterol acyltransferase, but failed to support cell growth despite rapid receptor mediated degradation even in the presence of low mevalonolactone concentrations. Inhibition of cholesterol esterification by Sandoz-Compound 58-035 enhanced cell growth in the presence of mevinolin, but did not promote proliferation in the additional presence of low-density lipoproteins. HDL3 but not HDL2 or tetranitromethane-modified HDL3 totally reversed the mevinolin induced inhibition of cell growth. This rescue by HDL3 was overcome by an increased dose of mevinolin. HDL3 derepressed reductase, stimulated cholesterol synthesis and reduced cholesterol esterification, but did not reverse the cholesterol synthesis inhibition by mevinolin. It is concluded that IEC-6 cells preferentially use endogenously synthesized cholesterol for membrane formation rather than low-density lipoprotein cholesterol. High-density lipoproteins appear to normalize cell growth in the presence of mevinolin by inhibition of cholesterol esterification and probably by inducing the formation of non sterol products of mevalonate.

Animals↗