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Biomedical subjects

N Walter

Publications and source records attributed to N Walter.

At least 19 recordsLinked to original sources
PubMed2004

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.

OBJECTIVE: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. METHODS: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was > or =20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). RESULTS: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p< or =0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p< or =0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p< or =0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p< or =0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (-0.29, -0.39, -0.38, -0.49 v -0.07; p< or =0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p< or =0.05). CONCLUSION: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Adalimumab↗
PubMed2000

A new betaA1-crystallin splice junction mutation in autosomal dominant cataract.

PURPOSE: To map the locus for autosomal dominant cataracts (ADCs) in a Brazilian family using candidate gene linkage analyses, describe the clinical variability, and identify potential mutations in the human betaA1-crystallin gene (CRYBA1), a candidate gene identified through linkage studies demonstrating cosegregation with markers on chromosome 17. METHODS: Members of a Brazilian family with ADC were studied. Clinical examinations and linkage analyses with polymerase chain reaction (PCR) polymorphisms of 22 anonymous markers and 2 within the neurofibromatosis type 1 gene were performed; two-point lod scores were calculated. DNA sequences of all 6 exons and 12 exon-intron boundaries of the betaA1-crystallin gene, a proximal candidate gene mapped to 17q11.1-q12 in one unaffected and two affected individuals, were screened and new variants assessed for cosegregation with the disease. RESULTS: Affected individuals exhibited variable expressivity of pulverulent opacities in the embryonal nucleus and sutures; star-shaped, shieldlike, or radial opacities in the posterior embryonal nucleus; and/or midcortical opacities. All known loci for ADC in this family on chromosomes 1 and 13 were excluded. A positive lod score on chromosome 17 was calculated. This ADC locus was mapped to two potential regions on the long arm with an intervening recombination. The only known candidate gene in these regions was betaA1-crystallin. Three previously unreported single nucleotide variants were found in this gene, one in the donor splice junction site of intron C. This variant was found in all affected members and is presumed to be the causative mutation. CONCLUSIONS: An ADC locus was mapped in a Brazilian family with variable expressivity to either 17q23.1-23.2 or 17q11.1-12 based on linkage analyses. Analyses of DNA sequences of the betaA1-crystallin gene in this family revealed three new variants, one of which is within a donor splice junction and cosegregates with affected members.

Base Sequence↗
PubMed1999

Suppressor analysis of the Saccharomyces cerevisiae gene REC104 reveals a genetic interaction with REC102.

REC104 is a gene required for the initiation of meiotic recombination in Saccharomyces cerevisiae. To better understand the role of REC104 in meiosis, we used an in vitro mutagenesis technique to create a set of temperature-conditional mutations in REC104 and used one ts allele (rec104-8) in a screen for high-copy suppressors. An increased dosage of the early exchange gene REC102 was found to suppress the conditional recombinational reduction in rec104-8 as well as in several other conditional rec104 alleles. However, no suppression was observed for a null allele of REC104, indicating that the suppression by REC102 is not "bypass" suppression. Overexpression of the early meiotic genes REC114, RAD50, HOP1, and RED1 fails to suppress any of the rec104 conditional alleles, indicating that the suppression might be specific to REC102.

Alleles↗
PubMed1998

Wide distribution of the cysteine string proteins in Drosophila tissues revealed by targeted mutagenesis.

The "cysteine string protein" (CSP) genes of higher eukaryotes code for a novel family of proteins characterized by a "J" domain and an unusual cysteine-rich region. Previous studies had localized the proteins in neuropil and synaptic terminals of larval and adult Drosophila and linked the temperature-sensitive paralysis of the mutants described here to conditional failure of synaptic transmission. We now use the null mutants as negative controls in order to reliably detect even low concentrations of CSPs by immunohistochemistry, employing three monoclonal antibodies. In wild-type flies high levels of cysteine string proteins are found not only in apparently all synaptic terminals of the embryonic, larval, and adult nervous systems, but also in the "tall cells" of the cardia, in the follicle cells of the ovary, in specific structures of the female spermatheca, and in the male testis and ejaculatory bulb. In addition, low levels of CSPs appear to be present in all tissues examined, including neuronal perikarya, axons, muscles, Malpighian tubules, and salivary glands. Western blots of isolated tissues demonstrate that of the four isoforms expressed in heads only the largest is found in non-neural organs. The wide expression of CSPs suggests that at least some of the various phenotypes of the null mutants observed at permissive temperatures, such as delayed development, short adult lifespan, modified electroretinogram, and optomotor behavior, may be caused by the lack of CSPs outside synaptic terminals.

Age Factors↗
PubMed1994

Paralysis and early death in cysteine string protein mutants of Drosophila.

Multimeric complexes of synaptic vesicle and terminal membrane proteins are important components of the neurotransmitter release mechanism. The csp gene of Drosophila encodes proteins homologous to synaptic vesicle proteins in Torpedo. Monoclonal antibodies demonstrate different distributions of isoforms at distinct subsets of terminals. Deletion of the csp gene in Drosophila causes a temperature-sensitive block of synaptic transmission, followed by paralysis and premature death.

Animals↗
PubMed1993

Fast chemiluminescent measurement of RNA polymerase activity based on photon counting technology.

A fast and simple assay for T7 RNA polymerase based upon chemiluminescent detection of the synthesized, digoxigenin-labeled RNA on a nylon membrane with anti-digoxigenin coupled alkaline phosphatase and CSPD as substrate is described. Activity of RNA polymerase is determined with high sensitivity by quantifying the emitted light of the microplate-formatted dot-blot membrane with a photon counting microplate luminometer and a specially designed filter adapter. The described method is one example for the application of this new adapter to measure luminescent membrane filters.

DNA-Directed RNA Polymerases↗
PubMed1989

Referrals from general practice to hospital outpatient departments: a strategy for improvement.

OBJECTIVE: To determine the appropriateness of referrals from general practice to hospital outpatient departments. DESIGN: Prospective audit of referrals from a group practice over one year. SETTING: Six handed practice in a southern coastal town. SUBJECTS: All patients referred during the study period for whom a copy of the referral letter was available. MAIN OUTCOME MEASURES: The investigations carried out by the consultant that led to the diagnosis; the diagnosis reached; and the management. RESULTS: Of roughly 3000 patients referred during the year, 277 with various skin and soft tissue disorders could probably have been managed solely by the general practitioner. Referrals for cryotherapy (96 in this series) and diabetes (19) could probably also have been avoided by specialist training of the general practitioner. In addition, in cases of haematuria and prostatic hypertrophy (34 and 22 referrals) substantial time could have been saved for both the patient and the consultant had the general practitioner supplied the results of relevant investigations. Probably the most important outcome was the model that the study offered for other general practitioners to improve the appropriateness of referrals. CONCLUSION: This approach to determining the appropriateness of referrals benefits the general practitioners, the consultant, and the patient.

England↗
PubMed1989

Granulomatous peritonitis caused by Ascaris eggs: a report of three cases.

Three cases of granulomatous peritonitis, due to the eggs of Ascaris lumbricoides, are reported. All patients presented with a palpable mass in the abdomen and two patients, in addition, had fever and abdominal pain. Laparotomy was performed and the operative diagnosis in each case was tuberculosis. The diagnosis of Ascaris ova peritonitis was made by histopathological examination of tissue removed at operation. The pathogenesis and differential diagnosis of this condition are briefly discussed.

Animals↗
PubMed1988

[A heated controversy--already settled today?].

In the sexuological literature there was a strong argument about the seeming inequality of clitorial or vaginal orgasms for a long time. S. Freud characterized the clitoral orgasm as immature, infantile and noted that it should be transformed into the advanced, truly vaginal orgasm. In contrast, feministically-oriented authors proclaimed the clitoral orgasm the actual, mentally more advanced one. Using a psychological "orgasm test" both hypotheses are verified in a population of 422 orgastically experienced women. The result shows that both clitoral and vaginal orgasms are not differently felt by women. Differently preferred coitus positions, either, are not supposed to have any influence on the orgastic experience of women.

Adult↗
PubMed1987

[Psychologic study of the female orgasm].

In contrast to the physiology of female orgasm the orgasm experience (the psychology of orgasm) has hardly been examined and not precisely been determined. In most cases descriptions of the experience are cited. A standardized procedure to estimate the frequency and intensity of symptoms recognized at orgasm is introduced here. The sample included 422 females aged from 18 to 50 years, among them 25 patients in psychotherapeutic settings and 23 twin pairs. Results show inter alia: large differences in the frequency of recognizing the different symptoms of orgasm (14 have been selected here). Three groups of symptoms are distinguished. A surprisingly low reflection of the muscle contractions in the mind. This problem is being discussed more in detail. What is the actual rating of the contractions of the orgastic ring? Multiorgastically reacting women observe all symptoms more often and intensively.

Adolescent↗
PubMed1979

[Vaccinia autoinoculata during pregnancy].

A 21 year old woman received a smallpox revaccination during the fifth to sixth month of pregnancy. She developed accidental vaccinia by autoinoculation and, five weeks later, gave birth to a healthy child.

Adult↗
PubMed1975

[Quantitative Cytochemical and Morphometric Investigations on Uterine Angiomatosis (Endolymphatis Stromal Myosis) and Stromal Sarcoma].

The angiomatosis uteri shows a low scattering of nuclear DNA content; an euploid DNA stem line suggests a benign behavior in these tumors. This evidence is supported by clinical experiences. The endometrial stromal sarcoma and the angioblastic sarcoma are characterized by a high scattering of nuclear DNA content, an aneuploid DNA stemline and a substantial irregularity of the nuclear area. These difference, suggest the malignancy of stromal and angioblastic sarcoma.

Adult↗