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Biomedical subjects

D Schmidt

Publications and source records attributed to D Schmidt.

At least 253 records · Page 14Linked to original sources
PubMed1995

The DnaK chaperone system of Escherichia coli: quaternary structures and interactions of the DnaK and GrpE components.

The DnaK (Hsp70), DnaJ, and GrpE heat shock proteins of Escherichia coli constitute a cellular chaperone system for protein folding. Substrate interactions are controlled by the ATPase activity of DnaK which itself is regulated by the nucleotide exchange factor GrpE. To understand the structure-function relationship of this chaperone system, the quaternary structures of DnaK, GrpE, and DnaK-GrpE complexes were analyzed by gel filtration chromatography, dynamic light scattering, analytical ultracentrifugation, and native gel electrophoresis. GrpE formed dimers in solution. DnaK formed monomers, dimers, and higher mole mass oligomers, the equilibrium between these forms being dependent on the DnaK concentration. The behavior of DnaK and GrpE in gel filtration and dynamic light scattering suggested elongated shapes of both molecules. In the absence of added nucleotides, DnaK and GrpE formed stable complexes containing one molecule of DnaK and two molecules of GrpE. A 44-kDa N-terminal ATPase fragment of DnaK also formed complexes with GrpE with the same 1:2 stoichiometry. DnaK-GrpE complex formation was unaffected by elimination of DnaK-bound nucleotides or addition of saturating concentrations of a DnaK peptide substrate. These findings allow the correlation of DnaK-GrpE interactions with a role for GrpE in the functional cycle of the DnaK chaperone system.

Adenosine Triphosphatases↗
PubMed1995

Electrocardiographic changes in patients with brain tumors.

OBJECTIVE: Electrocardiographic (ECG) abnormalities in patients with cerebral tumors involving the limbic system without known organic heart disease. DESIGN: Retrospective survey. SETTING: A university hospital in Berlin, Germany. PATIENTS: From among 169 consecutive patients with brain tumors, 57 patients were excluded on the basis of preexisting cardiac or other diseases and 27 patients were excluded because neuroimaging revealed multiple lesions or suggestive evidence of raised intracranial pressure. MAIN OUTCOME MEASURES: We compared ECG changes in 85 otherwise healthy patients with limbic and extralimbic brain tumors without evidence of increased intracranial pressure. Tumors were localized by magnetic resonance imaging and, in 15 cases, by computed tomography. Categorization of patients into limbic and extralimbic system groups was specified before routine preoperative ECGs were examined and classified by an independent cardiologist. RESULTS: Electrocardiographic changes were found in 40% of all patients. Abnormal ECG results were associated nearly three times more often with tumors located in the limbic system compared with extralimbic locations (72% vs 27%). Prolonged QTc intervals were significantly more frequent in the limbic system group than in the extralimbic group (mean rates, 113.3% vs 103.6%). CONCLUSIONS: Lesions of limbic structures do exert cardioarrhythmogenic effects and may provide an explanation for ECG abnormalities in patients with cerebral tumors.

Adult↗
PubMed1995

Retinal vascular hamartoma in von Hippel-Lindau disease.

OBJECTIVE: To diagnose von Hippel-Lindau disease at an early stage in the presence of atypical retinal lesions. DESIGN: Case series. METHODS: In an 11-year interdisciplinary clinical follow-up study of von Hippel-Lindau disease, 52 patients with retinal angiomas were investigated. RESULTS: Besides retinal angiomas, in five patients with von Hippel-Lindau disease or in the close relatives of such patients, unusual retinal vascular hamartomas other than retinal angiomas were detected. Retinal hamartomas are characterized by small, moss fiber-like, relatively flat vascular lesions with smooth and occasionally irregular margins and without enlarged afferent and efferent vessels. They are located within the superficial retina, usually adjacent to a retinal vein. In addition to typical peripheral retinal angiomas, a 28-year-old man with a pheochromocytoma had a treelike hamartoma. In another family, a brother and sister both had circumscribed red hamartomas with irregular outlines close to the retinal vessels. On fluorescein angiography, the early arterial filling of the hamartomas in two of these patients was striking. CONCLUSION: It is prudent to be aware of these unusual vascular retinal changes in von Hippel-Lindau disease. They may occur in isolation without additional retinal angiomas (as in four of our patients) but may suggest the presence of von Hippel-Lindau disease.

Adolescent↗
PubMed1995

Fasting and postprandial cerebrospinal fluid glucose concentrations in healthy women and in an obese binge eater.

OBJECTIVE: We hypothesized that abnormal entry of glucose into the central nervous system (CNS) might exist in some chronic binge eaters of carbohydrates, as either a cause or consequence of binge eating. The purpose of this study was thus to determine fasting and postprandial glucose concentrations in the cerebrospinal fluid (CSF) of healthy women, and to obtain similar data in an obese, irritable woman with chronic binge eating of postpartum onset. METHOD: CSF was sampled continuously at 0.1 ml/min from 1100 hr to 1700 hr from the binge eating patient, who consumed 5,000 to 10,000 calories per day (preferentially binging on refined carbohydrates), and 4 healthy women via an indwelling, flexible spinal canal catheter. CSF aliquots were obtained at 10-min intervals for measurement of glucose concentrations. Simultaneously, blood was withdrawn at 30-min intervals to obtain serum for glucose assay. A glucose-rich mixed liquid meal was consumed by participants at 1300 hr. RESULTS: In striking contrast to the normal women, our bulimic patient showed no postprandial rise whatever in CSF glucose concentrations. Fasting CSF glucose concentrations were slightly lower whereas fasting serum glucose levels were normal in the bulimic patient, compared with the normal women. After eating, serum glucose levels increased in all participants, but less so in our patient. DISCUSSION: This is the first description of a lack of postprandial elevation in CSF glucose concentration in a patient with a binge eating disorder. Defective transport of glucose across the blood-brain barrier might account for the observed abnormality. While considering other possibilities, we conjecture that our patient's binge eating was an attempt to compensate for impaired postprandial entry of glucose into her CNS.

Adult↗
PubMed1995

Effect of simvastatin on Lp(a) concentrations.

The effect of HMG-CoA reductase inhibitors on Lp(a) concentrations is controversial, with some studies showing an increase and others showing no effect on Lp(a) concentrations. Many of these studies have been limited by small sample size and the lack of a prospective design. We evaluated the effect of four treatments: (1) placebo, (2) simvastatin 10 mg PO QPM, (3) simvastatin 20 mg PO QAM, and (4) simvastatin 20 mg PO QPM on Lp(a) concentrations in a prospective, randomized, controlled clinical trial of 24 weeks in 343 subjects in 28 clinical sites in the United States. Simvastatin was not associated with a change in Lp(a) concentrations relative to placebo. These results were not affected by controlling for race, initial Lp(a) level, or urinary albumin excretion. Simvastatin significantly reduced low-density lipoprotein (LDL) cholesterol levels (10 mg PO QPM: -27.6%; 20 mg PO QAM: -28.1%; and 20 mg PO QPM: -34.3%, all p < 0.001). It was concluded that in a large, randomized, controlled trial, simvastatin does not affect Lp(a) levels but markedly lowers LDL cholesterol levels.

Adolescent↗
PubMed1995

Pharyngosellar pituitary: a rare developmental anomaly of the pituitary gland.

A rare malformation of the pituitary gland, termed pharyngosellar pituitary, is reported. The anterior pituitary gland was continuous from the pharyngeal roof to the sella turcica. This was found in a male fetus of gestational week 17 with an encephalocele and amnion adhesion malformation syndrome. The distribution of hormone-producing cells in the malformed pituitary tissue was irregular: thyrotropic hormone-, follicle-stimulating hormone- and luteinizing hormone-producing cells were nearly absent in the sellar and middle sections of the pituitary but were found in small numbers mainly in the pharyngeal section of the pituitary. The teratogenic determination period was estimated at between weeks 4 and 8 of gestation.

Abnormalities, Multiple↗
PubMed1995

Vacuum phenomena in insufficiency fractures of the sacrum.

OBJECTIVE: Insufficiency fractures of the sacrum are found in women who have undergone radiation therapy to the lower abdomen as well as those suffering from osteoporosis of postmenopausal, steroid-induced, or primary biliary cirrhosis-related origin. Increased uptake in bone scintigraphy and osteolytic changes in these fractures can be misinterpreted as bone metastases, leading to unnecessary biopsies and other procedures in the ensuing search for non-existent primary tumor. PATIENTS: In eight female patients averaging 69.4 years of age, insufficiency fracture of the sacrum was diagnosed by computed tomography (CT) and bone scintigraphy. Three underwent a total of five MRI examinations. Malignancy was excluded by histology in two patients and follow-up of at least 6 months in the remainder. Retrospective analysis of CT scans of 13 patients with metastases in the sacrum revealed no vacuum phenomena. RESULTS: In seven of eight patients with insufficiency fracture of the sacrum, vacuum phenomena were shown on CT examination. The gas was localized centrally within the ventral part of the fracture in three patients; gas was located in ten adjacent sacro-iliac joints of six patients. CONCLUSIONS: The vacuum phenomenon may be an incidental finding in osteoarthritis of the sacro-iliac joint, but it has not been previously recognized in IFS. The presence of intra-articular vacuum phenomena in the sacro-iliac joints in combination with a sacral fracture and vacuum phenomena located within the sacral fracture supports a diagnosis of insufficiency fracture or may indeed be the clue by which this diagnosis is established.

Aged↗
PubMed1995

[Placental site trophoblastic tumor. Morphology, differential diagnosis and prognosis].

A placental-site trophoblastic tumor is a rare neoplasia that is derived from the cells of the intermediate trophoblast. Morphological, biochemical, and Doppler ultrasound findings are presented regarding differential diagnosis using material from three recent cases. Essentially, placental-site trophoblastic tumors can be diagnosed if infiltration of the myometrium is seen by a monomorphic trophoblastic proliferation that is not interrupted by decidual cells. Necrosis and hemorrhages are not features of placental-site trophoblastic tumors. However, there is a peculiar behavior towards the uterine vasculature as spiral arteries are dilated and transformed the same way as occurs at the site of physiological implantation of pregnancy. It appears that as a result of this phenomenon there is a characteristic finding in ultrasound. Examination of this type of tumor demonstrates cystic spaces that can be defined as blood vessels by their Doppler signal. In two of the three cases a hysterectomy was performed, and criteria for the assumption of malignant placental-site tumors are therefore presented. However, only the mitosis rate seems to possess some predictive value.

Adult↗
PubMed1995

Carcinoma of the uterine cervix associated with schistosomiasis and induced by human papillomaviruses.

OBJECTIVES: To determine the presence of human papillomaviruses (HPVs) in cervical cancer among patients in Tanzania and to ascertain their prevalence in cases associated with schistosomiasis. METHODS: In situ hybridization was applied to 31 carcinomas of the uterine cervix including 10 in which schistosomiasis co-occurred. Twenty-six cases in this series also exhibited koilocytic dysplasia. RESULTS: Twenty-six out of 31 cases revealed a specific hybridization for HPVs with varying density and distribution. A slightly higher labeling of HPV-16 than -18 was demonstrated. All schistosomiasis-associated cancers encoded the papillomaviruses. The 31 patients were predominantly young adults, a fact that reflects sexual activity at a very young age in the ethnic communities of Africa. CONCLUSION: These findings shed new light on the presumed etiologic implication of schistosomiasis in the genesis of cervical cancer. In the absence of HPV, schistosomiasis is not the oncogenic causative agent for carcinoma of the uterine cervix.

Carcinoma, Squamous Cell↗
PubMed1995

Pharmacokinetics and bioavailability of rhIGF-I/IGFBP-3 in the rat and monkey.

Circulating IGF-I exists primarily as part of a ternary 150 kDa complex comprising equimolar amounts of IGF-I, IGFBP-3 and acid labile subunit (ALS). It is also known that in contrast to IGF-I and IGFBP-3 there exists a substantial quantity of unbound ALS in the circulation. As part of our preclinical development program, we have investigated the pharmacokinetic properties of a complex of human recombinant IGF-I and IGFBP-3. Systematic administration of rhIGF-I/IGFBP-3 results in binding of this binary complex to endogenous free ALS and thus leads to increased circulating levels of 150 kD ternary complex (IGF-I/IGFBP-3/ALS). In contrast to the administration of free IGF-I, IGF-I/IGFBP-3 dosing leads to increased systemic IGF-I exposure (i.e. increased area under the time vs. serum concentration curve or AUC) and decreased clearance (CL). Upon administration of equimolar doses of IGF-I/IGFBP-3 to the rat and monkey, it was found that in the monkey AUC was increased and CL decreased when compared to the rat. In addition, the pharmacokinetic profile suggests that saturation of excess ALS occurs at considerably lower doses of rhIGF-I/IGFBP-3 in the monkey than in the rat. Finally, the bioavailability of rhIGF-I/IGFBP-3 was assessed in the rat and found to be approximately 85% and 50% after intramuscular and sub-cutaneous administration, respectively. It was concluded that the formation of the 150 kD ternary complex had a significant impact on increasing the systemic exposure to rhIGF-I when administered as the binary complex (rhIGF-I/IGFBP-3). In addition, IGFBP-3 increases the therapeutic index of rhIGF-I even at doses that significantly exceed the saturation of ALS.

Animals↗
PubMed1995

The use of CD31 and collagen IV as vascular markers. A study of 56 vascular lesions.

A monoclonal antibody against the endothelial cell adhesion molecule CD31 (endo-CAM, PECAM-1) was tested on wax embedded tissue of 56 cases of vascular lesions including benign and malignant vascular neoplasms. Additional preparations were stained with antibodies to type IV collagen and to von Willebrand factor/Factor VIII-RAG (vWf). Our results prove reliability of CD31 and its superiority to vWf in the labelling of endothelium and its subsets in such lesions, with the exception of lymphangiomas. As markers for basal lamina collagen and endothelium respectively, type IV collagen and CD31 together provide a powerful tool for 1) the diagnosis of endothelial neoplasms and 2) the definition of endothelial, mural and pericytic or perivascular tissue compartments in vascular lesions of complex architecture. Hence, we use CD31 and type IV collagen in cases of presumed vascular neoplasms, adding other markers to the panel in accordance with the differential diagnosis, as well as in the recognition of compromised endothelia, such as in vascular invasion by various malignant neoplasms.

Antigens, Differentiation, Myelomonocytic↗
PubMed1995

A biotechnological method provides access to aggregation competent monomeric Alzheimer's 1-42 residue amyloid peptide.

Senile plaques, a neuropathological hallmark of Alzheimer's disease, consist primarily of insoluble aggregates of beta-amyloid peptide (A beta). A 42-residue peptide (A beta 1-42) appears to be the predominant form. In contrast to A beta 1-40, A beta 1-42 is characterized by its extreme tendency to aggregate into fibers or precipitate. A tailored biotechnological method prevents aggregation of A beta 1-42 monomers during its production. The method is based on a protein tail fused to the amino terminus of A beta. This tail leads to a high expression in E. coli, and a histidine affinity tag facilitates purification. Selective cleavage of the fusion tail is performed with cyanogen bromide by immobilizing the fusion protein on a reversed phase chromatography column. Cleavage then occurs only at the methionine positioned at the designed site but not at the methionine contained in the membrane anchor sequence of A beta. Furthermore, immobilization prevents aggregation of cleaved A beta. Elution from the HPLC column and all succeeding purification steps are optimized to preserve A beta 1-42 as a monomer. Solutions of monomeric A beta 1-42 spontaneously aggregate into fibers within hours. This permits the investigation of the transition of monomers into fibers and the correlation of physico-chemical properties with biological activities. Mutations of A beta 1-42 at position 35 influence the aggregation properties. Wild-type A beta 1-42 with methionine at position 35 has similar properties as A beta with a methionine sulfoxide residue. The fiber formation tendency, however, is reduced when position 35 is occupied by a glutamine, serine, leucine, or a glutamic acid residue.

Amino Acid Sequence↗
PubMed1995

[Measuring the death of invasion of endometrial carcinoma. Preoperative transvaginal ultrasound and correlation with intraoperative and histopathologic findings--a prospective study].

AIM: Determination of the correlation of the assessment of depth of invasion in endometrial cancer by transvaginal ultrasound, and by intraoperative assessment with histopathology. METHOD: In this study 25 patients with endometrial cancer diagnosed by dilatation and curettage were examined by means of transvaginal ultrasound. The sonographically assessed depth of invasion (inner or outer half of the uterus wall) was compared with the intraoperatively determined depth of invasion in the sectioned uterus. Finally, we correlated these findings with histopathology. RESULTS: Transvaginal ultrasound and the intraoperative assessment of depth of invasion had and accuracy of 80% if correlated with the definitive histopathology. The result of the frozen section was correct in all analysed cases. We also evaluated the wrong assessments in the ultrasound group and in those patients who were assessed intraoperatively. In all these cases there were additional pathological findings, such as polyps, fibroids and uterus retroflexus. CONCLUSION: We conclude that especially in such cases frozen section analyses yield helpful information on the depth of invasion and should be performed routinely.

Adult↗
PubMed1995

Genetics.

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Humans↗
PubMed1995

Behavioural abnormalities and retention rates of anti-epilepsy drugs during long-term treatment of epilepsy: a clinical perspective.

Vigabatrin is among the most promising of the new anti-epilepsy drugs, but two unrelated complications have been noted in patients receiving vigabatrin for chronic refractory epilepsy. These are, transient behavioural abnormalities and falling numbers of patients continuing to take vigabatrin (decreasing retention rate) during long-term treatment. Psychotic reactions have been carefully documented both in patients receiving standard and new anti-epilepsy drugs, and in up to 6% of patients after epilepsy surgery. As many psychotic episodes are associated with a dramatic cessation of seizures (i.e. high efficacy of treatment), it is not surprising that behavioural abnormalities are more often seen in patients receiving higher, more effective doses of vigabatrin, particularly those taking more than 3 g/day. A gradual dose increase and slow withdrawal is recommended for possible prevention of behavioural abnormalities, at least in some patients. During treatment with standard anti-epilepsy drugs, approximately 50% of patients remain on randomized treatment with the same drug for several years. For oxcarbazepine, a new drug, the figure is 60%, and for vigabatrin it is about 50%. Although comparative trials are not available, the retention rate for vigabatrin does not appear to be strikingly different to that reported for conventional anti-epilepsy drugs. In summary, behavioural abnormalities and falling retention rates appear to be general features of chronic epilepsy, and are certainly not exclusively associated with the use of vigabatrin. Controlled trials are required to establish the specific contribution, if any, of vigabatrin in development of these complications of intractable epilepsy.

Anticonvulsants↗