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M Binder

Publications and source records attributed to M Binder.

At least 181 records · Page 10Linked to original sources

Expression of the IV (reversed and/or heterotaxic) phenotype in SWV mice.

Approximately 50% of iv/iv mice have situs inversus (mirror image reversal of viscera) and 40% have heterotaxia (anomalous arrangement of viscera). The occurrence of heterotaxia is independent of situs. Using the cross-intercross breeding system to put the iv gene on the SWV background, an occasional presumed iv/+ mouse was found that had an IV (situs inversus and/or heterotaxic) phenotype. Testcrosses of these reversed animals indicated an iv/+ genotype. Since iv is linked tightly to Igh-C on chromosome 12, we inferred the genotype with a polymorphism of Igh-C demonstrated using the polymerase chain reaction (PCR). This confirmed them to be iv/+. The expression of the IV phenotype in animals heterozygous for the iv gene may be due to an interaction of iv with an autosomal recessive gene found in SWV. We have not found the IV phenotype in heterozygous iv/+ mice following placement of the iv gene on six other inbred strains. Rarely, we also found that presumed SWV +/+ mice had the IV phenotype. Test matings of these phenodeviants, corroborated by PCR, have confirmed them to be +/+. Although the phenotypes of the affected SWV +/+ and iv/+ mice resembled those found in iv/iv mice, the occurrence of situs inversus and heterotaxia were not independent of each other, and most of the SWV mice with the IV phenotype had heterotaxia with situs solitus. This infrequent dominant expression of the iv gene has so far only been seen when iv is on the SWV background. These findings are consistent with the idea that this phenomenon is due to the interaction of the iv gene with another gene found so far only in the SWV strain.

Animals↗

When applied to facial skin, does estrogen ointment have systemic effects?

We examined cytological vaginal smears of 17 women before and after three months of dermal estrogen (1 g of 0.01% estradiol ointment or 0.3% estriol ointment once daily), applied to the face for dermatological indications. The mean age was 57.1 +/- 7.6 years (range from 46 to 66). Seven women had estrogenic smears (more than 10% superficial cells) before therapy. Nine women were treated with 0.01% estradiol ointment and 8 were treated with 0.3% estriol ointment. Both groups had gynecological examinations including cervical and vaginal smears before and after treatment and also monthly measurements of serum follicle-stimulating hormone, prolactin and estradiol levels. Serum hormone levels and the appearance of vaginal smears showed no significant change during treatment.

Aged↗

Statistical evaluation of epiluminescence microscopy criteria for melanocytic pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive technique by which the clinical diagnosis of pigmented skin lesions (PSL) can be improved. Many ELM criteria have been described, but their significance in the differential diagnosis of PSL has not yet been established. OBJECTIVE: The purpose of this study was to determine the value of ELM criteria in the differential diagnosis of PSL. METHODS: Two hundred one melanocytic PSL (61 common nevi, 60 dysplastic nevi, and 80 melanomas) were investigated with ELM for the presence of certain ELM criteria; their significance was determined by calculating the odds ratios. RESULTS: Individual ELM criteria have different weights of significance in the differential diagnosis of melanocytic PSL. Selected patterns of ELM criteria adjusted to the distinct types of PSL considerably improve the diagnostic accuracy of melanocytic PSL. CONCLUSION: The prevalence of certain distinct ELM criteria in a given melanocytic PSL has statistical value in differential diagnosis.

Confidence Intervals↗

Two independent peroxisomal targeting signals in catalase A of Saccharomyces cerevisiae.

In contrast to many other peroxisomal proteins catalase A contains at least two peroxisomal targeting signals each sufficient to direct reporter proteins to peroxisomes. One of them resides at the extreme carboxy terminus constituting a new variant of this signal, -SSNSKF, not active in monkey kidney cells (Gould, S. J., G. A. Keller, N. Hosken, J. Wilkinson, and S. Subramani 1989. J. Cell Biol. 108:1657-1664). However, this signal is completely dispensable for import of catalase A itself. In its amino-terminal third this protein contains another peroxisomal targeting signal sufficient to direct reporter proteins into microbodies. This internal signal depends on the context. The nature of this targeting signal might be a short defined sequence or a structural feature recognized by import factors. In addition, we have demonstrated that the carboxy-terminal seven amino acids of citrate synthase of Saccharomyces cerevisiae encoded by CIT2 and containing the canonical -SKL represents a targeting signal sufficient to direct reporter proteins to peroxisomes.

Amino Acid Sequence↗

In vivo epiluminescence microscopy: improvement of early diagnosis of melanoma.

The majority of pigmented skin lesions can be diagnosed correctly on the basis of clinical criteria; however, there remain a surprisingly high number of small pigmented lesions in which the distinction between melanocytic and non-melanocytic and benign and malignant lesions, and thus between melanoma and non-melanoma, is difficult or impossible to make with the naked eye. Epiluminescence microscopy is a non-invasive technique that, by use of oil immersion, makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented lesions. The technique of epiluminescence microscopy is reviewed, and the significant improvement in the clinical diagnosis of pigmented skin lesions and, in particular, melanoma by this technique is documented.

Humans↗

Early recognition and prognostic markers of melanoma.

Malignant melanoma can be cured if the tumour is recognized at an early phase. Therefore, early recognition is of critical importance and cannot be overemphasized. Epiluminescence microscopy is a non-invasive technique that makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented skin lesions. Thereby preoperative clinical diagnosis can be improved. In order to assess the prognosis of a melanoma patient and to predict the outcome of the disease a number of morphological and immunological parameters these will be reviewed, are helpful.

DNA↗

Control of peroxisome proliferation in Saccharomyces cerevisiae by ADR1, SNF1 (CAT1, CCR1) and SNF4 (CAT3).

The Saccharomyces cerevisiae ADR1 gene has recently been demonstrated to control transcription of several genes encoding peroxisomal proteins or proteins necessary for peroxisome formation. Therefore, the effect of two other genes (SNF1 (CAT1, CCR1) and SNF4 (CAT3)) known to control derepression of glucose-repressible genes was studied. Levels of transcripts of genes encoding catalase A, fatty acid beta-oxidation enzymes and of the PAS1 gene are reduced in snf1 and snf4 mutants on ethanol as well as on oleic acid medium. By immunogold labelling with an antibody directed against peroxisomal thiolase, clusters of peroxisomes were detected in wild-type cells, whereas smaller single peroxisomes were observed in adr1 mutant cells. Results of immunofluorescence experiments are consistent with these observations. No peroxisomes were detected in snf1 and snf4 mutants by immunogold labelling as well as by immunofluorescence.

Acetyl-CoA C-Acetyltransferase↗

Humoral immune response against a 70-kilodalton heat shock protein of Entamoeba histolytica in a group of patients with invasive amoebiasis.

In order to investigate the humoral immune response against Entamoeba histolytica a lambda ZapII cDNA library was constructed from trophozoites of the pathogenic E. histolytica strain SFL-3. The library was screened with serum IgG from a patient with invasive amoebiasis. Forty-nine immunopositive lambda clones were isolated and partial sequences from the inserts were obtained. By comparison of the sequences with the merged database MIPSX from the Martinsried Institute for Protein Sequences we were able to identify homologous proteins for 36 of the clones. Twenty-six of the clones encoded intracellular proteins, among these, the major part (16 clones) were highly homologous to the eukaryotic 70-kDa heat shock proteins (Hsps). The open reading frame of one complete clone encodes a protein of 656 amino acid residues of 71.5 kDa which has 69.8% sequence identity with the human Hsp70 protein. In a larger screening experiment only 3 out of 12 patients detected with their IgG the phage which expressed the 70-kDa heat shock protein(s).

Amino Acid Sequence↗

Severe sun sensitivity and the presence of antinuclear antibodies in patients with polymorphous light eruption-like lesions. A form fruste of photosensitive lupus erythematosus?

BACKGROUND: Initial lesions seen in some cases of lupus erythematosus may simulate the clinical features of polymorphous light eruption. OBJECTIVE: To evaluate the significance of antinuclear antibody screening in patients with polymorphous light eruption or to find better methods to define patients at risk to have lupus erythematosus, we analyzed the data of 198 patients with polymorphous light eruption. METHODS: History, type, and persistence of skin lesions were reviewed, and serologic variables, the minimal erythema dose, and the ultraviolet action spectrum for inducing skin lesions were determined. RESULTS: The morphologic features of skin lesions and results of phototesting were consistent with previously published characteristics of patients with polymorphous light eruption. Twenty-eight (14%) had high titers of antinuclear antibody (greater than or equal to 1:80). We found a highly significant correlation between severe sun sensitivity and the presence of high antinuclear antibody titers. Of these patients with severe sun sensitivity and high titers of antinuclear antibody, in three the diagnosis of systemic lupus erythematosus could be established according to American Rheumatism Association criteria. CONCLUSION: These results suggest that a combination of severe sun sensitivity and high titers of antinuclear antibody may characterize a subset of sun-sensitive patients with some features of lupus erythematosus.

Adult↗

Pigmented Spitz nevi: improvement of the diagnostic accuracy by epiluminescence microscopy.

BACKGROUND: Pigmented Spitz nevi have distinct clinical features but often may be difficult to differentiate from malignant melanoma by clinical criteria. OBJECTIVE: The purpose of this study was to use a new noninvasive diagnostic approach to improve the clinical diagnosis of Spitz nevi. METHODS: Epiluminescence microscopy (ELM) is a new, noninvasive technique for which criteria for the diagnosis of melanocytic tumors, benign and malignant, recently have been established. These criteria were tested in an investigation of 54 pigmented Spitz nevi. RESULTS: With ELM the accuracy of clinical diagnosis of pigmented Spitz nevi improved from 56% (clinical) to 93% (ELM). CONCLUSION: Our findings suggest that ELM criteria are useful to improve the accuracy of clinical diagnosis of Spitz nevi.

Diagnosis, Differential↗

Fotemustine plus dacarbazine in advanced stage III malignant melanoma.

19 patients with advanced malignant melanoma were treated with fotemustine and dacarbazine. Data recorded and available for evaluation in all patients included clinical and histopathological parameters of the primary melanoma, blood chemistry, blood cell count, chest X-ray, ultrasound and bone scan for initial staging of the site of metastases and follow-up during treatment. Dosage was fotemustine 100 mg/m2 and dacarbazine 200 mg/m2 intravenously twice monthly on days 1 and 8, repeated for a maximum of six courses. There were two complete and three partial responses in 5/19 patients (26%), and 8 patients (42%) had stable disease. 6 (32%) patients had no response. Median length of complete and partial responses was 3.9 months, and that of stable disease 4.2 months. The main side-effects were thrombocytopenia in 10 patients (53%) and nausea in 6 (32%); the nausea was easily suppressed by ondasetron. Thus, fotemustine-dacarbazine may be new treatment in advanced melanoma.

Adult↗

Stereologic estimation of volume-weighted mean nuclear volume as a predictor of prognosis in "thin" malignant melanoma.

At present, tumor invasion represents the most reliable prognostic factor for primary malignant melanoma. The 10-year survival rate of "thin" melanomas (Breslow less than 0.76 mm) is more than 95%, but approximately 5% of these low-risk tumors do metastasize. In an attempt to determine prognostic markers for "thin" melanomas we investigated the volume-weighted mean nuclear volume (Vv) of primary melanomas with tumor invasions below 0.76 mm in 32 patients. Ten of these patients had developed melanoma metastases within a mean follow-up period of 49 months; 22 patients who had not developed metastases and who were comparable with regard to clinical and histologic criteria as well as to follow-up period were selected as a comparison group. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on hematoxylin-eosin-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. In addition, two-dimensional morphometric parameters (nuclear area and shape factors) as well as clinical (sex, age, location) and histologic characteristics (Breslow's thickness, Clark's level, and growth patterns) were recorded. The mean Vv (+/- SD) of primary melanomas with subsequent metastatic course was 273 microns 3 (+/- 81.3), whereas primary melanoma lesions without subsequent metastases exhibited a significantly lower Vv of 154 microns 3 (+/- 25.3) (p = 0.0008). On the other hand, two-dimensional morphometric and clinical and histologic parameters did not correlate with prognosis. Vv thus seems to represent a powerful and independent prognostic marker for "thin" primary melanomas. Assessment of Vv may provide a valuable tool in selecting patients with high-risk stage I, Breslow less than 0.76 mm, melanoma for adjuvant therapy.

Adult↗

Molecular characterization of IgG and IgE antigens of Entamoeba histolytica.

Several surface IgG antigens of E. histolytica have been characterized. We isolated two novel cDNAs by screening a library of pathogenic E. histolytica with rabbit antiserum against a membrane preparation of pathogenic amebas. cDNA K15 encodes a large protein > 220 kDa with sequence homology to myosins and K18 encodes a protein of around 40 kDa. Serum IgG from patients suffering from amebiasis binds to both antigens. Some IgE antibodies are able to recognize homologous proteins in all eukaryotes investigated. We demonstrate that IgE antibodies from pollen allergic patients bind to plant, human, as well as E. histolytica profilins.

Allergens↗

Cyclic amplification and selection of targets (CASTing) for the myogenin consensus binding site.

The consensus binding site for the muscle regulatory factor myogenin was determined from an unbiased set of degenerate oligonucleotides using CASTing (cyclic amplification and selection of targets). Stretches of totally random sequence flanked by polymerase chain reaction priming sequences were mixed with purified myogenin or myotube nuclear extracts, DNA-protein complexes were immunoprecipitated with an antimyogenin antibody, and the DNA was amplified by polymerase chain reaction. Specific binding was obtained after four to six cycles of CASTing. The population of selected binding sites was then cloned, and a consensus was determined from sequencing individual isolates. Starting from a pool with 14 random bases, purified myogenin yielded a consensus binding site of AACAG[T/C]TGTT, while nuclear extracts retrieved the sequence TTGCACCTGTTNNTT from a pool containing 35 random bases. The latter sequence is consistent with that predicted from combining an E12/E47 half-site (N[not T]CAC) with the purified myogenin half-site ([T/C] TGTT). The presence of paired E boxes in many of the sequences isolated following CASTing with nuclear extracts proves that myogenin can bind cooperatively with other E-box-binding factors.

Animals↗

Vector-mediated overexpression of catalase A in the yeast Saccharomyces cerevisiae induces inclusion body formation.

To study the morphological effects of overexpression of catalase A in yeast, the gene coding for catalase A was introduced into Saccharomyces cerevisiae on a multicopy vector. After induction of microbody biogenesis and catalase A expression by growth on oleic acid as sole carbon source, cells were analyzed by immunofluorescence and immunoelectron microscopy. In addition, overexpression of catalase A was studied by quantitative immunoblotting and by activity measurement. Quantitative immunoblotting resulted in a 16-fold difference between immunoreactive material from transformed and non-transformed cells. An 18-fold increase of enzyme activity was measured in transformed cells due to overexpression of catalase A from plasmid pAH521. Immunofluorescent staining of semithin sections of Lowicryl HM20-embedded cells with anti-catalase localized peroxisomes and--at a low percentage--larger particles. By immunoelectron microscopy, these larger structures could be identified as agranular, electron-dense aggregates which are morphologically clearly distinct from the cytoplasm and not bounded by a membrane. These structures, which have been named inclusion bodies, contain catalase A but not other peroxisomal enzymes like thiolase. These findings suggest that cells are capable of compensating for overproduced proteins by formation of particular types of structures.

Acetyl-CoA C-Acetyltransferase↗

Fate of highly expressed proteins destined to peroxisomes in Saccharomyces cerevisiae.

Import of proteins into organelles usually requires a cis-acting targeting signal. Analysis of various hybrid proteins, consisting of mouse DHFR and parts of catalase A from Saccharomyces cerevisiae, revealed that fusion proteins containing the N-terminal 126 amino acids, or less, of catalase A remain in the cytosol whereas fusion proteins containing 140, or more, N-terminal amino acids of catalase A form large aggregates inside the cell. These protein bodies, which lack a surrounding membrane, copurified with peroxisomes on cell fractionation. The peroxisomal targeting signal of catalase A does not reside at the C-terminus or at the N-terminus.

Amino Acid Sequence↗

Elective regional lymph node dissection in malignant melanoma.

In patients with malignant melanoma elective regional lymph node dissection (ELND) is controversial. This retrospective study evaluated differences in prognosis in patients who were treated with or without ELND. 168 patients were included who initially presented with stage I melanoma (without palpable regional lymph nodes), and who had a minimum observation period of at least 5 years, or had died of malignant melanoma within 5 years of diagnosis. In 66 patients a wide local excision (WLE) followed by ELND was done. In 102 cases only a WLE was done. Assignment of patients to the two groups was non-random but there was no significant difference in age, sex, type and location of primary tumour and depth of invasion. No significant difference was found in survival of the two groups. The 5 year survival of the WLE group was 85.7% and that of the WLE plus ELND group was 89.1%. The 10 year survival rate was 77.9% and 73.1%, respectively. Neither in the whole series nor after sub-division of the patients into three classes according to Breslow depth of invasion (up to 1.5, 1.51-2.5, and greater than 2.5 mm) was a significant influence of ELND on the survival of patients apparent. Cox's regression model did not show ELND as a prognostic factor. ELND cannot be recommended as a routine treatment in patients with stage I melanoma.

Adult↗