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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 343 records · Page 19Linked to original sources
PubMed1995

Severe, irreversible renal failure after ifosfamide treatment. A clinicopathologic report of two patients.

BACKGROUND: Chronic renal failure has been described only rarely in patients treated with the alkylating agent ifosfamide, which is known to cause renal tubular dysfunction and acute renal failure, and the associated histopathologic features have not been well characterized. METHODS: This report describes the clinical course and renal histopathologic features in two patients in whom irreversible renal failure occurred requiring permanent dialysis after treatment with ifosfamide. RESULTS: Irreversible renal failure developed in a 60-year-old man with malignant fibrohistiocytoma, requiring chronic dialysis within several months after he received two cycles of ifosfamide in a cumulative dose of 28 g/m2. The second patient, a 53-year-old man with osteogenic sarcoma, received two cycles of ifosfamide with a cumulative dose of 26 g/m2, after initial therapy with cisplatin and doxorubicin. His renal function worsened over the next 11 months, at which time permanent dialysis was initiated. In neither patient were other causes of renal failure apparent. Renal biopsies in both patients showed diffuse tubular epithelial damage with degenerative and regenerative epithelial changes, diffuse interstitial fibrosis, and arterial and arteriolar sclerosis. CONCLUSIONS: Irreversible severe renal failure, which appears due to nephrotoxic damage of renal tubular epithelium and/or the renal microvasculature may develop after treatment with ifosfamide. Neither large cumulative doses of ifosfamide nor prior cisplatin treatment are necessary for this toxicity to occur. Because a rising serum creatinine may develop months after completion of treatment with ifosfamide, renal function should be monitored closely both during and after ifosfamide treatment.

Antineoplastic Agents, Alkylating↗
PubMed1995

Construction and characterization of a Rhizobium leguminosarum biovar viciae strain designed to assess horizontal gene transfer in the environment.

An integration vector was developed which inserts cloned DNA in a non-essential site of the Rhizobium leguminosarum biovar viciae chromosome. The expression of integrated genes is under the control of the constitutive neomycin phosphotransferase II (nptII) promoter of transposon Tn5. The design of the vector ensures that loss of vector sequences can be detected, enabling selection of progeny containing only the requisite DNA. The newly constructed vector was employed to insert the Escherichia coli gusA gene conferring GUS activity into R. leguminosarum bv. viciae strain LRS39401 which is cured of its symbiotic plasmid (pSym). One GUS-positive transconjugant, strain CT0370, was shown to have lost all vector sequences. Conjugal transfer of pSym2004 (a Tn5-tagged derivative of symbiotic plasmid pRL1JI, which specifies pea nodulation and symbiotic nitrogen fixation) to CT0370, restored the GUS-positive strain's symbiotic proficiency. Strain CT0370 is presently being used in a field release experiment in order to assess the extent of pSym transfer in a natural R. leguminosarum bv. viciae population under environmental conditions.

Base Sequence↗
PubMed1995

Cell-adhesion molecules in memory formation.

After learning events the CNS of higher organisms selects, which acquired informations are permanently stored as a memory trace. This period of memory consolidation is susceptible to interference by biochemical inhibitors of transcription and translation. Ependymin is a specific CNS glycoprotein functionally involved in memory consolidation in goldfish: after active shock-avoidance conditioning ependymin mRNA is rapidly induced in meningeal fibroblasts followed by enhanced synthesis and secretion of several closely related forms of the protein. Intracranial injections of anti-ependymin antisera or antisense oligodeoxynucleotides interfere specifically with memory consolidation, indicating that only de novo synthesized ependymin molecules are involved. Ependymin is capable of directing the growth of central axons in vitro and participates in neuronal regeneration in situ, presumably by its HNK-1 cell-adhesion epitope. Experiments reviewed in this article suggest a model that involves two regulation mechanisms for the function of ependymin in behavioural plasticity: while hormones appear to determine, how much of this cell adhesion molecule is synthesized after learning, local changes of metal cation concentrations in the micro-environment of activated neurons may polymerize ependymin at those synapses, that have to be consolidated to improve their efficacy for future use.

Animals↗
PubMed1995

Magnetic resonance imaging cerebral abnormalities and neuropsychologic test performance in elderly hypertensive subjects. A case-control study.

OBJECTIVE: To search for a morphologic basis of cognitive impairment possibly associated with arterial hypertension using magnetic resonance imaging and a demanding neuropsychologic test battery. DESIGN: Case-control comparison with age, length of education, presence of diabetes, and presence of cardiac disease as matching criteria. SETTING: Austrian Stroke Prevention Study. SUBJECTS: A total of 89 hypertensive subjects and 89 control subjects from a subset of 272 volunteers with no neurologic symptoms undergoing extensive diagnostic workup in a large-scale stroke prevention study among randomly selected elderly community members. MAIN OUTCOME MEASURES: Focal brain abnormalities and size of ventricles and cortical sulci as assessed by magnetic resonance imaging and neuropsychological test scores. RESULTS: Hypertensive subjects more commonly showed areas of white matter hyperintensity and moderately severe ventricular enlargement compared with controls. While no differences were noted between the investigational groups in test results of memory capacity and conceptualization, hypertensive subjects tended to perform worse when assessed for attentional and visuopractical skills. These differences became significant when comparing the brain-damaged subsets of patients and controls with their counterparts without cerebral changes. The pattern and extent of neuropsychologic deficits was similar in hypertensive and normotensive subjects with abnormal magnetic resonance imaging scans. CONCLUSION: Our data strongly suggest the high rate of brain abnormalities among hypertensive subjects as the cause of their subtle neuropsychological dysfunction.

Aged↗
PubMed1995

MR pulsatility measurements in peripheral arteries: preliminary results.

Phase contrast flow velocity measurements were performed in six healthy volunteers and 30 patients with arteriosclerotic disease. The iliac arteries were investigated in 8 cases and the femoral arteries in 28 cases. In the first 24 patients, 16 evenly distributed data sets were acquired during one cardiac cycle. In the last 12 patients, a trigger pulse followed by the acquisition of 30 evenly distributed data sets was applied every second heart beat. This procedure allowed data to be acquired over a full heart cycle without any acquisition gap. The measured flow velocities were displayed as function of time. Systolic acceleration, postsystolic deceleration and pulsatility of flow velocity were calculated and compared with stenosis grades determined from DSA angiograms. Flattening of the flow velocity patterns was found to correlate with the local severity of arteriosclerotic disease.

Adult↗
PubMed1995

Delayed responses to electrical stimuli reflect C-fiber responsiveness in human microneurography.

The slowing of impulse conduction during the relative refractory period has often been used to assess activation of C-fibers, in particular, in human microneurography. This study aimed to evaluate the sensitivity of this method and the factors affecting it. Thirty cutaneous C-fibers were recorded from the peroneal nerves of healthy human subjects. Intracutaneous electrical stimulation in the receptive field at 4 s intervals, after some minutes of adaptation, induced spike discharges at constant latency. One or more conditioning stimulus pulses were interpolated at different intervals and the increase in latency after the subsequent regular pulse was assessed. The latency shift was found to depend on the number of interposed pulses, on the time interval between conditioning and conditioned stimulus, and on the conduction velocity of the C-unit. The increase in latency was larger with greater distance between stimulating and recording electrodes, indicating a contribution of the conductile membrane over its whole length. On the other hand, slowing was more pronounced, on average, in slower conducting C-units and conduction velocities were slower when recordings were performed more distally. These findings indicate that the slower terminal nerve branches contribute most to the latency increases. Even a single additional spike in between two regular pulses caused a reliable latency shift of 1.2 +/- 0.2 ms (mean +/- SEM) and additional pulses lead to an approximately linear latency increase (2 pulses: 2.3 +/- 0.3 ms; 4 pulses: 5.9 +/- 0.7 ms). In contrast to the number of interposed stimuli, different intervals between interposed and regular stimuli had only a minor impact on the latency shifts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Toxicity of Fusarium sambucinum Fuckel sensu lato to brine shrimp.

In a screening test seven Fusarium strains out of 17 proved to be toxic towards brine shrimp. Among these, four F. sambucinum strains as well as three F. venenatum isolates caused toxic effects. The chemical screening by TLC analysis revealed the presence of sambucinol and diacetoxyscirpenol in the extracts of the toxic isolates of F. venenatum 64537.

Animals↗
PubMed1995

Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment.

Although both morphologic cerebral damage and cognitive dysfunction are known to occur in patients on chronic hemodialysis (CHD) their extent and possible relation have been rarely studied. We therefore performed magnetic resonance imaging of the brain and neuropsychological testing in 30 consecutive CHD patients (mean age 58 years; range 37-69) and in an equal number of asymptomatic volunteers matched for age, sex and major cerebrovascular risk factors. Twenty-four (80%) of the CHD patients were demented according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders IIIR and their mean scores on the Mini Mental State Examination (22.9 +/- 4 vs. 27.9 +/- 1.4; p < 0.001) and Mattis Dementia Rating Scale (112.3 +/- 21.5 vs. 141.9 +/- 2.3); p < 0.001) were significantly lower than those of controls. The brains of CHD patients showed significantly more atrophy on visual rating and semiquantitative morphometric measures. Multiple lacunes or confluent white matter hyperintensities predominated in 10 (33%) patients, three showed territorial infarcts and two a combination of both. Clinically these findings were unexpected in almost half of individuals. Marked cognitive impairment was associated with more extensive enlargement of the third ventricle (5.8 +/- 1.8 vs. 7.3 +/- 2 mm; p < 0.04) and the temporal horns (3.5 +/- 1.6 vs. 5.1 +/- 1.8 mm; p < 0.02) but not with the presence of cerebral ischemic lesions or any difference in laboratory data. These results call attention to a very high rate of cerebral damage in individuals undergoing CHD and suggest brain degeneration of probably toxic-metabolic etiology to be associated with severe cognitive impairment of these patients.

Adult↗
PubMed1995

Elbow extension using anterior deltoids and upper pectorals in spinal cord-injured subjects.

OBJECTIVE: Surface electromyography was used to identify muscles active in isometric elbow extension in spinal cord-injured (SCI) patients. DESIGN: Tetraplegic subjects participated in this cohort study aimed at identifying some of the muscles that are active during isometric elbow extension. SETTING: Regional Spinal Cord Injury (SCI) Center. PATIENTS: The patients had to have a C6 motor level on the right side (wrist extensor > or = 3/5) with 0/5 or 1/5 elbow extensor muscle power. Of 32 patients who could be contacted by telephone, 6 eventually were able to make it to the SCI center for testing. MEASUREMENTS: The patients performed a series of isometric elbow extension contractions of 25%, 50%, and 75% of maximum voluntary contraction (MVC) as measured by a force transducer. Surface electromyography (EMG) of the right elbow extensor, anterior deltoid, and upper pectoral muscles was measured using the root mean square (rms) of the amplitude of the motor unit activity as the parameter of muscle activity. Statistical analyses were performed using a repeated analysis of variance (ANOVA) with Tukey post-hoc HSD for each percentage of MVC. RESULTS: For each muscle tested, there was significantly (p < 0.05) greater rms activity for each percentage of MVC except between 50% and 75% MVC of the elbow extensor muscle. However, the elbow extensor muscle had minimal EMG activity when compared with the amplitude of the rms activity of the anterior deltoid and upper pectoral muscles for each percentage of MVC. CONCLUSION: The results of the study suggest that the anterior deltoid and the upper pectoral muscles exert an isometric elbow extension force for C6 quadriplegic patients.

Adult↗
PubMed1995

Patient selection for breast conservation therapy with magnification mammography.

BACKGROUND: Breast-conserving therapy (BCT) is an appropriate treatment for women with breast carcinoma of limited extent. This study was undertaken to determine the ability of microfocal spot magnification mammography to identify women with multifocal or multicentric breast carcinoma who were unlikely to have all gross carcinoma removed with a limited breast resection. METHODS: Two hundred sixty-three women with mammographically visible ductal carcinoma in situ and stage 1 and 2 carcinoma who were clinical candidates for BCT were evaluated with magnification mammography before undergoing definitive local therapy. Biopsy specimens of additional abnormalities thought to have a greater than 2% risk of malignancy were obtained. RESULTS: Forty-seven women had other abnormalities in the index breast requiring intervention, and 216 had only the primary tumor identified. Mean age, cancer presentation, disease stage, and histologic tumor type did not differ between groups. BCT was successful in 97.2% of women without mammographic abnormalities versus 38% of women with abnormalities (p = 0.001). Clinical characteristics did not differ between patients undergoing successful BCT and those requiring mastectomy. Synchronous contralateral carcinoma was identified in 2.4% of women at risk. CONCLUSIONS: Magnification mammography allows accurate preoperative identification of patients requiring mastectomy or quadrantectomy and should be performed before diagnostic biopsy is done.

Adult↗
PubMed1995

Effective and less toxic reversal of low-molecular weight heparin anticoagulation by a designer variant of protamine.

PURPOSE: This investigation assessed protamine reversal of heparin anticoagulation by formation of a protamine-heparin alpha-helix by use of a new designer-variant protamine [+18BE] that was made from an existing protamine variant [+18B] whose non-alpha-helix-forming amino acid proline (P) was replaced by an alpha-helix-forming glutamic acid (E). The rate of administration of the new [+18BE] variant protamine on efficacy and toxicity in comparison to that of [+21] standard protamine and [+18B] was also studied. METHODS: Acetyl-EAA(K2A2K2A)4K2-Amide [+18BE] was administered intravenously in a 1:1 dose to low-molecular-weight heparin (LMWH)-anticoagulated (intravenous 150 IU antifactor Xa/kg) dogs over 10 seconds or 3 minutes (n = 7, each group). Reversal efficacy was documented by measuring activated clotting time, thrombin clotting time, antifactor Xa, and antifactor IIa. Toxicity was defined by measuring systemic blood pressure, heart rate, cardiac output, pulmonary artery pressure, and oxygen consumption. Measurements were made at baseline, after administration of LMWH, before its reversal, and for 30 minutes thereafter. Results were compared with those after LMWH reversal with [+21] standard protamine and the [+18B] variant. A total toxicity score (TTS) was calculated for each compound from maximal declines in blood pressure, heart rate, cardiac output, and oxygen consumption. RESULTS: LMWH anticoagulation reversal was significantly (p < 0.01) less toxic over 10 seconds and 3 minutes with the [+18BE] designer variant (TTS -2.3, -2.2) compared with the [+21] standard protamine (TTS -6.4, -7.2). Percent LMWH reversal at 3 minutes revealed [+18BE] to have antifactor Xa activity as high as 91%, compared with 68% for protamine [+21], when given over 3 minutes (p < 0.05). CONCLUSIONS: This investigation documents that a new designer variant of protamine [+18BE] has superior efficacy compared with [+21] standard protamine for reversal of LMWH anticoagulation and that this occurs with a highly favorable toxicity profile.

Amino Acid Sequence↗
PubMed1995

Learning-induced expression of meningeal ependymin mRNA and demonstration of ependymin in neurons and glial cells.

The turnover of a CNS-specific cell adhesion glycoprotein, ependymin, has earlier been found to increase during periods of neuronal plasticity. Here, ependymin mRNA expression was analyzed by semiquantitative in situ hybridization in goldfish. Learning of an active avoidance response resulted in a significant increase in ependymin mRNA expression 20 min to 4 h after acquisition of the task. In contrast, yoked control animals that were exposed to the same numbers of conditioned and unconditioned stimuli in a random, unpaired manner exhibited a strong down-regulation of ependymin mRNA. Hybridization signals were also increased by injection of anti-ependymin antiserum into brain ventricles. Ependymin mRNA was exclusively localized to reticular-shaped fibroblasts of the inner endomeningeal cell layer. Immunoelectron microscopic investigation, however, revealed ependymin also in distinct neuronal and glial cell populations in which no ependymin mRNA had been detected. Uptake of meningeal protein factors into glial and neuronal cells may therefore be of functional importance for plastic adaptations of the CNS.

Animals↗
PubMed1995

Inhibition of memory consolidation after active avoidance conditioning by antisense intervention with ependymin gene expression.

A rapid increase in ependymin mRNA expression demonstrated by semiquantitative in situ hybridization after avoidance conditioning on goldfish suggested a molecular demand for newly synthesized ependymin translation product. To inhibit de novo synthesis of ependymin molecules without interference with preexisting ones, 18 mer anti-ependymin mRNA-phosphorothioate oligodeoxynucleotides (S-ODNs) were injected into the perimeningeal brain fluid before active avoidance training. S-ODN-injected animals learned the avoidance response; however, they were amnesic in the test. When injected into overtrained animals, S-ODNs did not interfere with retrieval or performance of the avoidance response. Fish treated with randomized S-ODN sequences served as further controls. Incorporation of S-ODNs was analyzed by injection of fluorescein isothiocyanate (FITC)-conjugated oligodeoxynucleotide probes. Microscopic observation revealed strong FITC-S-ODN fluorescence in reticular-shaped fibroblasts, the only known site of ependymin synthesis. Results demonstrate that selective inhibition of ependymin gene expression in vivo can specifically prevent memory formation. We conclude that in particular the newly synthesized ependymin molecules are involved in memory consolidation, possibly because they have not yet undergone irreversible molecular changes, which have been reported of this glycoprotein in a low-calcium microenvironment.

Animals↗
PubMed1995

[Peripheral occlusive arterial diseases: comparison of diagnostic value of MRA and DSA].

MATERIAL AND METHODS: In 59 patients with arterial flow disturbances 2-D inflow sequence of the abdominal and lower leg arteries were prospectively obtained on a 1.5 T MR-imager and were compared with additional DSA examinations. Supplementary Phase Contraste RSE ("Rapid Sequential Excitation") sequences were carried out in 29 patients. MRA and DSA angiograms were evaluated in random order by 4 readers using a questionnaire. The assessment of image quality were evaluated by variance analysis. Diagnostic performance of MRA and DSA was assessed by comparison of the readers' diagnostic assessments with reference diagnoses established by a radiologist and a vascular surgeon with full knowledge of all data concerning a patient. Image quality of inflow MRA was considered inferior to i.a. DSA (p < 0.001) and comparable with i.v. DSA (p = 0.1361). Image quality of RSE-MRA was inadequate (p < 0.001). Correspondingly, i.a. DSA was the superior and RSE-MRA the inferior imaging technique. The accuracy of inflow MRA in determining stenosis grade was 66% and that of RSE-MRA 59%.

Aged↗
PubMed1995

Endothelium-modulated proliferation of medial smooth muscle cells: influence of angiotensin II and converting enzyme inhibition.

This study investigated the role of the endothelium and angiotensin II (Ang II) in regulating medial smooth muscle cell (SMC) proliferation. [3H]-thymidine incorporation into medial SMC of rat arteries was examined in vivo, using ballooned rat carotid arteries, as well as in vitro, using cultures of aortic tissue rings (organoids). In vivo, maximal medial [3H]-thymidine incorporation occurred within 3 days post-ballooning. In endothelium-denuded organoids, maximum medial DNA synthesis was achieved after 7 days of culture. [3H]-thymidine-labelling of SMC in intact organoids (with endothelium) increased minimally during culture, indicating that the endothelium provided protection with respect to medial proliferation under basal conditions (culture in the presence of 1% plasma-derived serum). Inclusion of 10(-7) M Ang II significantly elevated medial [3H]-thymidine incorporation above that in control cultures. The stimulatory effect of Ang II was much more pronounced in intact organoids that in endothelium-denuded organoids, indicating synergistic growth regulation by Ang II and endothelium-derived factors. When organoids were cultured in the combined presence of Ang II and the ACE inhibitor cilazaprilat, labelling indices of intact organoids were also significantly increased above control, but to a lower level than those obtained in the presence of Ang II alone. However, for endothelium-denuded organoids, medial [3H]-thymidine incorporation in the combined presence of Ang II and cilazaprilat was not significantly different from that in untreated controls. Thus, cilazaprilat exerts both endothelium-dependent and endothelium-independent negative regulatory effects on medial SMC proliferation.

Angiotensin II↗
PubMed1995

Arabidopsis phosphoribosylanthranilate isomerase: molecular genetic analysis of triplicate tryptophan pathway genes.

Phosphoribosylanthranilate isomerase (PAI) catalyzes the third step of the tryptophan biosynthetic pathway. Arabidopsis PAI cDNAs were cloned from a cDNA expression library by complementation of an Escherichia coli trpC- PAI deficiency mutation. Genomic DNA blot hybridization analysis detected three nonallelic genes encoding PAI in the Arabidopsis genome. DNA sequence analysis of cDNA and genomic clones indicated that the PAI1 and PAI2. All three PAI polypeptides possess an N-terminal putative plastid target sequence, suggesting that these enzymes all function in plastids. The PAI1 gene is flanked by nearly identical direct repeats of approximately 350 nucleotides. Our results indicate that, in contrast to most microorganisms, the Arabidopsis PAI protein is not fused with indole-3-glycerolphosphate synthase, which catalyzes the next step in the pathway. Yeast artificial chromosome hybridization studies indicated that the PAI2 gene is tightly linked to the anthranilate synthase alpha subunit 1 (ASA1) gene on chromosome 5. PAI1 was mapped to the top of chromosome 1 using recombinant inbred lines, and PAI3 is loosely linked to PAI1. cDNA restriction mapping and sequencing and RNA gel blot hybridization analysis indicated that all three genes are transcribed in wild-type plants. The expression of antisense PAI1 RNA significantly reduced the immunologically observable PAI protein and enzyme activity in transgenic plants. The plants expressing antisense RNA also showed two phenotypes consistent with a block early in the pathway: blue fluorescence under UV light and resistance to the anthranilate analog 6-methylanthranilate. The extreme nucleotide conservation between the unlinked PAI1 and PAI2 loci suggests that this gene family is actively evolving.

Aldose-Ketose Isomerases↗
PubMed1995

Properties of the carcinoma-associated antigen MH 99/KS 1/4 in normal and transformed human keratinocytes: regulation of synthesis, molecular cross-linking and ultrastructural localization.

A 38-kDa cell-surface glycoprotein defined by monoclonal antibody MH 99 is markedly increased in many epithelial tumours. In normal human skin, it is a characteristic marker for germ-cell phenotypic tissues. Although the gene encoding the MH 99 antigen has recently been cloned, and several histological and biochemical studies have been performed, the biological function of this interesting antigen still remains unknown. In the present study, we examined the synthesis of MH 99 in keratinocyte populations showing different in vitro differentiation capacity. Normal keratinocytes, spontaneously immortalized keratinocytes (cell line HaCaT), three SV-40-transformed keratinocyte lines (130, 425, and HaSV), and two squamous cell carcinoma lines (SCL-1 and SCL-2), were compared. Radioimmunoprecipitation revealed the highest levels of synthesis in cell populations with the least differentiation. This was paralleled by an increase of MH 99 synthesis in normal keratinocytes cultured in low concentrations of Ca2+ and by an increase of MH 99 synthesis during subculture of normal keratinocytes. Both phenomena were paralleled by an opposite behaviour of a differentiation marker. Molecular cross-linking and subsequent immunoprecipitation led to a decrease of the MH 99 signal, but an increase of a high molecular weight protein signal was seen. After cleavage of the crosslinker, the MH 99 signal reappeared, whereas the signal of the large protein remained unchanged. Thus, the MH 99 antigen may be associated with a high molecular weight protein on the cell surface, supporting the suggestion of a receptor-like function. Phosphorylation of the molecule could not be detected. Immunoelectron microscopy revealed homogeneous distribution on the cell surface, but cells of the same culture exhibited clear differences in their MH 99 expression. A concept for MH 99 regulation in normal and transformed human keratinocyte populations in vitro is proposed, showing that the synthesis of MH 99 is inversely correlated with cell differentiation. The association with a high molecular weight protein supports the suggestion that the MH 99 antigen interacts with other molecules.

Antibodies, Monoclonal↗