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Biomedical subjects

E Weiss

Publications and source records attributed to E Weiss.

At least 55 records · Page 3Linked to original sources
PubMed1999

Mgm101p is a novel component of the mitochondrial nucleoid that binds DNA and is required for the repair of oxidatively damaged mitochondrial DNA.

Maintenance of mitochondrial DNA (mtDNA) during cell division is required for progeny to be respiratory competent. Maintenance involves the replication, repair, assembly, segregation, and partitioning of the mitochondrial nucleoid. MGM101 has been identified as a gene essential for mtDNA maintenance in S. cerevisiae, but its role is unknown. Using liquid chromatography coupled with tandem mass spectrometry, we identified Mgm101p as a component of highly enriched nucleoids, suggesting that it plays a nucleoid-specific role in maintenance. Subcellular fractionation, indirect immunofluorescence and GFP tagging show that Mgm101p is exclusively associated with the mitochondrial nucleoid structure in cells. Furthermore, DNA affinity chromatography of nucleoid extracts indicates that Mgm101p binds to DNA, suggesting that its nucleoid localization is in part due to this activity. Phenotypic analysis of cells containing a temperature sensitive mgm101 allele suggests that Mgm101p is not involved in mtDNA packaging, segregation, partitioning or required for ongoing mtDNA replication. We examined Mgm101p's role in mtDNA repair. As compared with wild-type cells, mgm101 cells were more sensitive to mtDNA damage induced by UV irradiation and were hypersensitive to mtDNA damage induced by gamma rays and H2O2 treatment. Thus, we propose that Mgm101p performs an essential function in the repair of oxidatively damaged mtDNA that is required for the maintenance of the mitochondrial genome.

Alleles↗
PubMed1999

Pathophysiologic basis of contrast enhancement in breast tumors.

While the diagnostic benefits of gadolinium (Gd)-chelate contrast agents are firmly established in magnetic resonance imaging (MRI) of tumors, the pathophysiologic basis of the enhancement observed and its histopathologic correlate remained vague. Tumor angiogenesis is fundamental for growth and metastasis and also of interest in new therapeutic concepts. By correlative analysis of a) histology; b) vascular density (CD31); and c) vascular permeability (vascular permeability factor/vascular endothelial growth factor [VPF/VEGF]), we found a) significantly (P < 0.001) faster exchange rates in malignant compared with benign breast lesions; b) distinct differences in enhancement characteristics between the histologic types (invasive ductal carcinoma, invasive lobular carcinoma, and ductal carcinoma in situ); and c) dependence of enhancement kinetics on the VPF/VEGF expression. The pathophysiologic basis for the differences in contrast enhancement patterns of tumors detectable by MRI is mainly due to vascular permeability, which leads to more characteristic differences than vascular density. MRI is able to subclassify malignant breast tumors due to their different angiogenetic properties.

Adult↗
PubMed1999

Therapeutic outcome and relation of acute and late side effects in the adjuvant radiotherapy of endometrial carcinoma stage I and II.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy is the standard treatment for endometrial carcinoma. However, until now there has been no clear indication that radiotherapy in that setting improves survival. This calls for critical assessment of the relation between the expected benefit and the number and severity of postradiotherapeutic side effects. MATERIAL AND METHODS: In a retrospective study 159 consecutive patients with stage I and II endometrial carcinoma were treated with external radiotherapy and vaginal brachytherapy after hysterectomy and bilateral salpingoophorectomy (no surgical lymph node staging). Recurrence rates, survival and side effects were evaluated, in particular with regard to the relation of acute and late toxicity. RESULTS: Five percent of all patients developed a recurrence either in the abdomen or at distant locations. No pelvic relapses were diagnosed. Five-year relapse-free survival was 92% for stage IA + B, 84% for stage IC, and 79% for stage II disease. Acute toxicity was seen in 65.4% of patients, all grade 1 or 2, late toxicity grade 1 or 2 in 18.8%, grade 3 or 4 complications in 1.8%. The estimated 5-year freedom from late toxicity was 76.8%. Seventy-seven percent of all patients with treatment interruptions or premature end of therapy experienced late injury. In ten of 33 patients with late sequelae there was no free interval between early and late toxicity. No relation of radiation technique/fractionation and the rate of side effects was noticed. CONCLUSIONS: Adjuvant radiotherapy leads to excellent pelvic control, with few serious complications. Major acute toxicity shows significant correlation with the incidence of severe late injury, which we suggest to classify in part as consequential late effects.

Adult↗
PubMed1999

PE-11, a peptide derived from chromogranin B, in the human brain.

This study was performed to investigate the distribution of chromogranin B in the human central nervous system. We used an antiserum raised against a synthetic peptide (PE-11) present in the chromogranin B molecule. PE-11-like immunoreactivity was characterized by molecular size exclusion and reversed-phase high-performance liquid chromatography. Its localization was studied using immunocytochemistry. Only the free peptide and an N-terminally elongated peptide were detected by molecular size exclusion high-performance liquid chromatography, indicating that proteolytic processing of chromogranin B is quite extensive. PE-11-like immunoreactivity was present in differently shaped fibers, varicosities and neurons, but not in glial cells. Its density varied throughout the brain. An especially high density was observed in the bed nucleus of the stria terminalis, the central and cortical nuclei of the amygdala, the hypothalamus, the hippocampus, the raphe complex, the nucleus interpeduncularis, the nucleus of the solitary tract, and laminae I and II of the spinal cord. This study demonstrates a significant processing of chromogranin B and indicates that chromogranin B constitutes a precursor for smaller peptides which are derived by endoproteolytic processing. It provides the neuroanatomical basis to investigate the chromogranin B molecule as a widespread component of large dense-core vesicles in the human central nervous system.

Adult↗
PubMed1999

Detection of soluble HLA-G molecules in plasma and amniotic fluid.

Although the cDNA sequence of HLA-G antigens is compatible with their expression as soluble molecules (sHLA-G), the determination of native sHLA-G levels in body fluids has not yet been described. The lack of this information is likely to reflect the difficulties in developing an assay suitable to measure sHLA-G antigens in the presence of soluble HLA-A, -B and -C (sHLA-I) antigens, since most of the available anti-HLA-G mAb do not detect soluble beta2-m associated HLA-G antigens or crossreact with sHLA-I antigens. Therefore, we have developed a two-step assay which eliminates the interference of classical HLA class I antigens. In the first step, the sample is depleted of sHLA-I antigens and of HLA-E antigens with mAb TP25.99. Then, HLA-G antigens are captured with mAb W6/32 and detected with anti-beta2-m mAb in ELISA. Utilizing this assay, sHLA-G antigen levels were measured in EDTA plasma from 92 controls with known HLA types, 28 women at delivery and the corresponding cord bloods and in 50 amniotic fluids. Mean sHLA-G plasma levels did not differ between males (24.9+/-3.0 SEM ng/ml; n=42) and females (20.1+/-2.1 SEM ng/ml; n = 50). However, sHLA-G levels in HLA-A11 positive probands (mean: 13.0+/-4.4 SEM ng/ml; n=12) were significantly (P<0.05) lower than in HLA-A11 negative ones (mean: 24.5+/-2.0 SEM ng/ml; n=80). sHLA-G levels in women at delivery (mean: 22.9+/-2.2 SEM ng/ml; n=28) were in the range of controls but were significantly (P<0.001) reduced in the corresponding cord bloods (mean: 13.8+/-1.5 SEM ng/ml; n=28). sHLA-G levels in amniotic fluids (mean: 15.5 + 1.0 SEM ng/ml; n=50) were significantly (P<0.001) lower than in plasma. sHLA-G levels were 5 and 11% of those of sHLA-I antigens in plasmas and amniotic fluids, respectively. Individual sHLA-G levels were not correlated with sHLA-I levels. SDS-PAGE analysis of plasma sHLA-G antigens revealed two molecular variants with a 35 kD and a 27 kD MW corresponding to the sizes of sHLA-G1 and -G2 isoforms. In conclusion, our study has shown that the two-step assay we have developed is reliable in measuring sHLA-G antigen levels. This assay will facilitate the analysis of the biological and clinical significance of sHLA-G antigens in plasma.

Adult↗
PubMed1999

Accuracy of alignment in breast irradiation: a retrospective analysis of clinical practice.

The objective of the study was to determine the accuracy of patient positioning in radiotherapy for breast cancer. Portal images were obtained using a fast electronic megavoltage radiotherapy imaging system in 30 cases of breast cancer. Quantitative analysis of 530 megavolt portal images and comparison with 30 digitized simulation films were performed. Five linear measurements were taken for each simulation and verification film. Central lung distance (CLD) is the distance from the dorsomedial beam edge to the inner thoracic wall in the central plane of the beam. Cranial lung distance (CrLD) is the distance from the dorsomedial beam edge to the inner thoracic wall in the plane of the beam at 4 cm from the central plane. Central beam edge to skin distance (CBESD) is the distance from the skin to the ventrolateral beam edge in the central plane of the beam. The central irradiated width (CIW) is defined as the distance from the dorsomedial beam edge to the skin. The craniocaudal distance (CCD) is defined as the distance from a particular landmark to the caudal field border. Concerning patient position in the field, mean standard deviations of the difference between simulation and treatment images were 3.9 mm for the CLD, 3.2 mm at +4 cm, 3.6 mm for the CIW, 3.3 mm for the CBESD, 3.8 mm for the CCD. In 90% of all set-up for treatment, errors were less than 1 cm. The variation of the CLD was the largest set-up error. This parameter is clinically the most significant. Future treatment delivery should be improved by introducing patient positioning devices such as thermoplastic shells. The electronic portal imaging device (EPID) appears to be an adequate tool to study the accuracy of treatment set-ups like this.

Breast Neoplasms↗
PubMed1998

Treatment of primary malignant rhabdoid tumor of the brain: report of three cases and review of the literature.

PURPOSE: Primary malignant rhabdoid tumor (MRT) of the central nervous system is an extremely aggressive tumor predominantly related to early childhood, with characteristic histopathological findings but unclear histogenesis. Owing to its low incidence, little knowledge exists concerning the best therapeutic strategy. METHODS AND MATERIALS: Three children of our hospital with MRT of the brain underwent a maximum tumor resection followed by multidrug chemotherapy and radiation therapy to the craniospinal axis. RESULTS: Relapse was disseminated along the spinal subarachnoid spaces in one child and occurred at the primary tumor site in the other two patients. Maximum survival was 15 months from diagnosis. CONCLUSION: A review of patients reported in the literature and a comparison to our patients reveals a high propensity to early local relapse and meningeal dissemination. In the absence of more effective therapeutic options, we recommend multidisciplinary treatment of patients in good general condition and with resectable disease. In particular, following radiation therapy, tumor remissions and delay of tumor regrowth have been observed.

Brain Neoplasms↗
PubMed1998

Expression of major histocompatibility complex class II antigen in neoplastic cells of canine cutaneous histiocytoma.

Forty five cases of canine cutaneous histiocytoma (CCH) were examined by immunohistology for expression and distribution of major histocompatibility complex (MHC) class II antigen in neoplastic cells. In addition, expression of lysozyme and calprotectin (leucocyte protein L1) in neoplastic cells was investigated. Furthermore, B and T lymphocytes were demonstrated by antibodies against the CD3 antigen, IgG, and IgM. Neoplastic cells showed two staining patterns for MHC class II antigen: focal juxtanuclear cytoplasmic staining and/or rim-like staining along the cell periphery. In 24 cases, a predominant or exclusive focal juxtanuclear cytoplasmic MHC class II antigen reaction in neoplastic cells, and the presence of few diffusely distributed infiltrating CD3 antigen-positive T lymphocytes were observed. Tumors with numerous neoplastic cells exhibiting staining for MHC class II antigen along the cell periphery (n = 21) showed increased inflammatory alterations, represented by disseminated and nodular infiltrations of mainly CD3 antigen-positive T cells. B cells, plasma cells, exudate macrophages, and neutrophils were rarely seen disseminated between neoplastic cells whereas their number increased within focal inflammatory infiltrates. The focal cytoplasmic reaction for MHC class II antigen in neoplastic cells might represent newly synthesized MHC class II molecules stored in vesicles, whereas staining of the cell periphery might occur due to accumulation of MHC class II molecules along the plasma membrane. The increasing expression of MHC class II molecules on the cell surface might be the decisive factor for onset and progression of tumor regression. However, the exact mechanism of priming and activation of T cells by neoplastic cells and the nature of the presented antigen are not yet known.

Animals↗
PubMed1998

Un-cross-linked fibrin substrates inhibit keratinocyte spreading and replication: correction with fibronectin and factor XIII cross-linking.

Wound repair is characterized by the presence of a fibrin-rich matrix, but the effect of fibrin on re-epithelialization remains unclear. In this study, we determined the effects of different fibrin matrices on cultured human neonatal keratinocytes. Using purified fibrinogen and fibrin gels generated by the enzymatic action of thrombin, batroxobin (it leads to retention of fibrinopeptide B), or Agkistrodon contortrix thrombin-like enzyme (ACTE; it leads to retention of fibrinopeptide A), we determined the effect of each of these matrices on keratinocyte morphology, attachment, spreading, and replication as compared to tissue culture plastic. Morphologically, keratinocytes seeded on fibrin surfaces were more rounded and formed three-dimensional structures. Specific cell attachment, as measured at either 37 degrees C or 4 degrees C, was not altered on the different fibrin substrates (P > .05) but was increased on fibrinogen and factor XIII cross-linked fibrin (P < .01). However, keratinocytes seeded on fibrin, regardless of the presence or absence of fibrinopeptides A or B, showed a marked decrease (up to 71%) in cell numbers by days 5 (P = .0357) and 10 (P = .0114). Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes. However, either the addition of fibronectin or cross-linking of fibrin with factor XIII allowed full keratinocyte spreading to occur (P = .0002 and P = .0013, respectively). We conclude that fibrin inhibits keratinocyte spreading in the absence of other matrix or plasma proteins or cross-linking by factor XIII.

Cell Adhesion↗
PubMed1998

Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy.

OBJECTIVE: This retrospective study was conducted to document the incidence and location of recurrences as well as the rate of side effects following low-dose postoperative high-dose-rate (HDR) brachytherapy in patients with endometrial carcinoma. METHODS: From 1987 to 1993, 122 patients with moderate-risk (78) and high-risk (44) endometrial carcinoma underwent adjuvant vaginal irradiation. All patients received three fractions of 7 Gy specified on the surface of the vaginal cylinder. RESULTS: Relapses occurred in 12 (9. 8%) patients on average after 25.6 months. Seven (5.7%) patients had a sole pelvic recurrence; in 2 (1.6%) of those the relapse was located in the vagina only. Three (2.5%) patients had a pelvic relapse combined with distant metastases. Distant metastases alone were diagnosed in 2 (1.6%) patients. A tumor recurrence was diagnosed in 3 of 78 (3.8%) patients with moderate-risk disease and in 9 of 44 (20.5%) patients with high-risk disease. The estimated 5-year relapse-free survival was 94% for patients with moderate-risk and 74% for patients with high-risk tumors (P = 0.004). Neither severe nor chronic complications were noted. CONCLUSION: Even low doses of HDR brachytherapy seem sufficient for excellent vaginal disease control in moderate-risk disease. In advanced tumors combined radiation therapy is warranted for improved pelvic disease control.

Aged↗
PubMed1998

Expression in Escherichia coli of Y5 mutant and N-terminal domain-deleted DNA gyrase B proteins affects strongly plasmid maintenance.

Escherichia coli DNA gyrase B subunit (GyrB) is composed of a 43-kDa N-terminal domain containing an ATP-binding site and a 47-kDa C-terminal domain involved in the interaction with the gyrase A subunit (GyrA). Site-directed mutagenesis was used to substitute, in both the entire GyrB subunit and its 43-kDa N-terminal fragment, the amino acid Y5 by either a serine (Y5S) or a phenylalanine residue (Y5F). Under standard conditions, cells bearing Y5S or Y5F mutant GyrB expression plasmids produced significantly less recombinant proteins than cells transformed with the wild-type plasmid. This dramatic decrease in expression of mutant GyrB proteins was not observed when the corresponding N-terminal 43 kDa mutant plasmids were used. Examination of the plasmid content of the transformed cells after induction showed that the Y5F and Y5S GyrB protein level was correlated with the plasmid copy number. By repressing tightly the promoter activity encoded by these expression vectors during cell growth, it was possible to restore the normal level of the mutant GyrB encoding plasmids in the transformed bacteria. Treatment with chloramphenicol before protein induction enabled large overexpression of the GyrB mutant Y5F and Y5S proteins. In addition, the decrease in plasmid copy number was also observed when the 47-kDa C-terminal fragment of the GyrB subunit was expressed in bacteria grown under standard culture conditions. Analysis of DNA supercoiling and relaxation activities in the presence of GyrA demonstrated that purified Y5-mutant GyrB proteins were deficient for ATP-dependent gyrase activities. Taken together, these results show that Y5F and Y5S mutant GyrB proteins, but not the corresponding 43-kDa N-terminal fragments, compete in vivo with the bacterial endogenous GyrB subunit of DNA gyrase, thereby reducing the plasmid copy number in the transformed bacteria by probably acting on the level of negative DNA supercoiling in vivo. This competition could be mediated by the presence of the intact 47-kDa C-terminal domain in the Y5F and Y5S mutant GyrB subunits. This study demonstrates also that the amino acid Y5 is a crucial residue for the expression of the gyrase B activity in vivo. Thus, our in vivo approach may also be useful for detecting other important amino acids for DNA gyrase activity, as mutations affecting the ATPase activity or GyrB/GyrB, or GyrB/GyrA protein interactions.

Binding Sites↗
PubMed1998

Management of extremely low birth weight infants: perceptions of viability and parental counseling practices.

OBJECTIVE: To determine physician opinions, parental counseling, and medical practices for extremely low birth weight (LBW) infants. METHODS: A retrospective survey was sent in August 1996 to 450 California physicians practicing obstetrics. RESULTS: There was a 41% response rate. The mean thresholds for antenatal steroid administration, cesarean delivery for fetal distress and delivery room resuscitation were gestational age between 23 and 24 weeks and weight close to 500 g. Most obstetricians counsel parents regarding survival, resuscitation, and possible death in the delivery room before delivery of an extremely LBW infant. Just over 60% of obstetricians believe that parents have a role in deciding not to resuscitate an infant born at 22 weeks' gestation, this decreases to less than 50% at 24 weeks, and decreases further to less than 30% by 26 weeks' gestation. Just over 40% of obstetricians report their counseling is affected by pediatric opinion, 33% by previous maternal perinatal losses, and less than 20% by maternal drug use or lack of prenatal care, and young maternal age. Language barriers, parental education level, and family insurance affect treatment options in less than 10% of obstetricians. CONCLUSION: Obstetric opinions about delivery room resuscitation of extremely LBW infants are influenced by birth weight and gestational age thresholds, infant, and parental factors. There is a limited willingness by physicians to allow a parental role in decision making in the delivery room for extremely LBW infants.

Adult↗
PubMed1998

Human complement factor H deficiency associated with hemolytic uremic syndrome.

This study reports on six cases of deficiency in the human complement regulatory protein Factor H (FH) in the context of an acute renal disease. Five of the cases were observed in children presenting with idiopathic hemolytic uremic syndrome (HUS). Two of the children exhibited a homozygous deficiency characterized by the absence of the 150-kD form of Factor H and the presence, upon immunoblotting, of the 42-kD Factor H-like protein 1 (FHL-1) and other FH-related protein (FHR) bands. Southern blot and PCR analysis of DNA of one patient with homozygous deficiency ruled out the presence of a large deletion of the FH gene as the underlying defect for the deficiency. The other four children presented with heterozygous deficiency and exhibited a normal immunoblotting pattern of proteins of the FH family. Factor H deficiency is the only complement deficiency associated with HUS. These observations suggest a role for FH and/or FH receptors in the pathogenesis of idiopathic HUS.

Acute Disease↗
PubMed1998

[Significance and possibilities of histopathologic diagnosis in breed-specific skin diseases].

An increasing number of punch biopsies is submitted for histopathology. Results are often disappointing for the veterinary pathologist as well as the referring veterinarian. Inappropriate timing of sampling, selection and preparation of the biopsy site, type of biopsy, biopsy technique and fixation as well as incomplete histories often contribute to insufficient diagnosis and interpretation of skin lesions. The introduction of this review gives an overview of the requirements for a satisfying evaluation of skin lesions and the limits of diagnostic histopathology on skin samples, especially punch biopsies. The second part summarizes more frequent dermatohistopathological diagnoses according to the pattern analysis of skin lesions, using examples of skin diseases with breed predisposition. Among the described skin lesions are the dermatoses associated with endocrine dysfunction, cutaneous mucinosis, Vogt-Koyanagi-Harada-like syndrome, alopecia of color mutants, dermatomyositis, granulomatous sebadentitis, Malassezia dermatitis, pyoderma and atopic dermatitis.

Animals↗