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Biomedical subjects

J Mueller

Publications and source records attributed to J Mueller.

At least 19 recordsLinked to original sources

Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): structure and results of a population-based registry.

The severe skin reactions erythema exsudativum multiforme majus (EEM with mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are difficult to study as they are very rare diseases with an incidence of about two cases per 1 million inhabitants per year. We report on the structure of a registry with the aim of ascertaining all hospitalized cases of EEMM, SJS, and TEN in western Germany and Berlin. The registry is structured as an intensive reporting system, regularly contacting more than 1500 departments including 100% of the burn units (n = 34), departments of pediatrics (n = 241), departments of dermatology (n = 106), and 100% of all internal medicine departments in hospitals with intensive care facilities or with more than 200 beds (n = 1161). With a coverage rate up to 95% based on the number of responding departments between April 1, 1990 and December 31, 1992, from a total of 767 reported cases 353 patients with EEMM, SJS, and TEN were finally included in the registry. Most of these patients were directly reported to the registry; only 2.54% (9 of 353) were primarily registered by the German spontaneous reporting systems. Assuming an average population of 64.5 million for western Germany and Berlin an incidence up to 1.89 per 1 million inhabitants per year could be calculated for SJS and TEN.

Epidemiologic Methods

School-based AIDS education for adolescents.

PURPOSE: To describe a program which utilizes medical students and persons with AIDS (PWAs) to provide for adolescents school-based education about acquired immunodeficiency syndrome (AIDS). METHODS: Two 1.5 hour classroom sessions were conducted by medical students and persons with AIDS for seventh and eighth grade students (n = 1,161 students) at two urban middle schools. In addition, a two hour informational session was provided for parents. A 49 question student health survey was used to evaluate adolescents' HIV knowledge, tolerance of persons with AIDS, and intentions to engage in human immunodeficiency virus (HIV) safe behaviors. RESULTS: Significant (p < 0.01) increases in HIV knowledge and tolerance of persons with AIDS were observed, which persisted for three months. A significant (p < 0.01) improvement in intention to engage in HIV-safe behaviors was observed but did not persist for three months. CONCLUSIONS: Medical students and persons with AIDS can provide school-based AIDS education to early adolescents.

Acquired Immunodeficiency Syndrome

Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history.

We analyzed 66 adenocarcinomas arising in the upper gastrointestinal tract for microsatellite instability at eight microsatellite loci to investigate the role of these genetic alterations in the etiology of these tumors. We identified alterations in at least one locus in 11/46 adenocarcinomas of the stomach, in 2/15 adenocarcinomas arising in Barrett's esophagus, and in 1/5 adenocarcinomas of the duodenum and jejunum. Microsatellite instability in gastric tumors was found in 5/22 of intestinal, 1/3 of mixed, and 5/21 of diffuse type tumors. No relationship to the tumor stage (TNM), age, and survival time of the patients was observed. One patient had two synchronous gastric tumors both exhibiting microsatellite instability at multiple loci. His family history revealed four individuals in the maternal line afflicted with gastric carcinoma in three generations. Our data show that microsatellite instability is a genetic event in 11 to 24% of tumors of the upper gastrointestinal tract. The observation of microsatellite instability and a familial clustering of gastric tumors may suggest a genetic predisposition for a subset of gastric tumors, which may be identified by microsatellite analysis.

Adenocarcinoma

In situ hybridization in pathology.

The technique of in situ hybridization (ISH) is presented with special reference to its use in the practice of pathology. Methodological and theoretical aspects of ISH are first considered with regard to tissue fixation, probe selection and preparation, various types of labeling reactions and aspects of hybridization conditions as they relate to hybridization protocols. This is followed by a discussion about the interpretation of the results of ISH with regard to sensitivity and specificity and the importance of, and various types of, controls. Lastly, specific applications of ISH in pathology are discussed, concluding with possible future applications for ISH in research and diagnosis.

Animals

Charcot-Marie-Tooth disease type 1A. Association with a spontaneous point mutation in the PMP22 gene.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy. CMT type 1A is associated with a 1.5-megabase DNA duplication in region p11.2-p12 of chromosome 17 in most patients. An increased dosage of a gene within the duplicated segment appears to cause the disease. The PMP22 gene, which encodes a myelin protein, has been mapped within the duplication and proposed as a candidate gene for CMT type 1A. METHODS: We analyzed DNA samples from a cohort of 32 unrelated patients with CMT type 1 who did not have the 1.5-Mb tandem duplication in 17p11.2-p12 for mutations within the PMP22 coding region. Molecular techniques included the polymerase chain reaction (PCR), heteroduplex analysis to detect point mutations, and direct nucleotide-sequence determination of amplified PCR products. RESULTS: A 10-year-old boy was identified with a point mutation in PMP22, which resulted in the substitution of cysteine for serine in a putative transmembrane domain of PMP22. Analysis of family members revealed that the PMP22 point mutation arose spontaneously and segregated with the CMT type 1 phenotype in an autosomal dominant pattern. The patients with the PMP22 point mutation had clinical and electrophysiologic phenotypes that were similar to those of patients with the 1.5-Mb duplication. CONCLUSIONS: The PMP22 gene has a causative role in CMT type 1. Either a point mutation in PMP22 or a duplication of the region including the PMP22 gene can result in the disease phenotype.

Amino Acid Sequence

High-specificity in-situ hybridization. Methods and application.

We describe a technique of in-situ hybridization using oligonucleotide probes employing the expression of immunoglobulin VH genes as a model. Optimal conditions for hybridization with the 35S-labeled oligonucleotide probes were established with monoclonal B-cell lines that express VH genes of known nucleic acid sequence. The range of sensitivity and specificity achieved with this technique is documented. Under conditions of high stringency, this method can detect the expression of highly related VH hypervariable regions.

B-Lymphocytes

Lesbian erotics: the utopian trope of Donne's "Sapho to Philaenis".

Famous for its self-assertive masculinity, John Donne's love poetry nonetheless includes a verse elegy which stands alone not only in his work but also in the entire literary production of the Renaissance for its celebration and defense of a passionate lesbian relation binding the two women of its title. No editorial grounds exist for denying Donne's authorship of "Sapho to Philaenis"; rather the interpretive task is to reconstitute the poem's significance in period terms. The task is complicated by Donne's penchant for flouting literary and social convention as he successively overturns Ovid's influential portrayal of Sappho as an aging voluptuary reclaimed for heterosexuality, the virulent homophobia of Renaissance humanists, and the coy idealizations and transient evocation given to lesbian affectivity by the very few Renaissance writers (including Shakespeare) who touched on the subject at all. When "Sapho to Philaenis" is set in the context of Donne's other love elegies in verse as productions by a young intellectual moving in sophisticated London circles and writing for a coterie audience, lesbianism looks like a master trope for positively resolving a dilemma that confounded Montaigne and many other authors of the age. Could the perfections of love and friendship be united in a relation of equality between two persons? Gender hierarchy and separate socialization precluded a heterosexual construction of any such equality in the Renaissance, and the greater opprobrium cast on male homosexuality in this era must have influenced Donne's decision to figure his equal lovers and friends as a lesbian couple. Yet the disclosive power of "Sapho to Philaenis" goes far beyond the entailments of a specific choice of poetic representation. Donne really undertakes to imagine the pleasures, sustenance, and ideological implications by which lesbianism, as a mode of loving and being, resists patriarchal disposition and diminution of women. Donne anticipates the advances of twentieth-century feminists (Colette, Kofman, Irigaray) as he poetically articulates possibilities and knowledge that were otherwise denied expression by Renaissance culture and its exponents.

England

Protection by U-50,488H against beta-chlornaltrexamine antagonism of nitrous oxide antinociception in mice.

Nitrous oxide antinociception in the abdominal constriction test was significantly reduced in mice pretreated intracerebroventricularly (i.c.v.) with beta-chlornaltrexamine (beta-CNA). However, this antagonism was reversed when the beta-CNA was co-administered i.c.v. with the kappa-opioid ligand U-50,488H but not the mu-opioid ligand CTOP. These findings further demonstrate that nitrous oxide antinociception in the mouse abdominal constriction paradigm is mediated by kappa- but not mu-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Vibrio vulnificus. Hazard on the half shell.

Vibrio vulnificus is an extremely invasive gram-negative bacillus that causes bacteremia and shock. It should be suspected in any patient who is immunocompromised or has liver disease or hemochromatosis. Reduced gastric acidity may also increase the risk of infection if a patient presents with a history of ingesting raw shellfish (especially oysters) or trauma in brackish waters and skin lesions. Patients most commonly present with one of three clinical syndromes: primary septicemia, wound infection, or gastroenteritis. Treatment includes aggressive wound debridement, antibiotic therapy, and supportive care. Rapidly diagnosing and promptly initiating therapy are critical because V vulnificus infection is rapidly progressive and mortality approaches 100% if septic shock occurs.

Animals

Schistosoma mansoni: experimental chemoprophylaxis in mice using oral anti-penetration agents.

The ability to prevent schistosomiasis by using an oral chemoprophylactic agent, which acts by preventing cercarial penetration, has been unexplored. We initially examined the effect of praziquantel (PZQ) as such an agent and found that it was moderately effective in blocking cercarial penetration, but that this effect was dependent on the vehicle used to administer the drug. ICR mice were given a total of 200 mg/kg PZQ per os over an 8-hr period in a divided dose of 50 mg/kg/2 hr. At time periods ranging from 0 to 92 hr after the last dose, mice were exposed to approximately 75 75Se-labeled cercariae via the tail. Twenty-four hours later, mice were sacrificed, their tails were removed and subjected to autoradiography, and the percentage of penetration was calculated. Cremophor El, 50% PEG 200, 50% propylene glycol, vegetable oil, and cod liver oil were used as PZQ vehicles. When Cremophor El (ethoxylated castor oil) was used to administer PZQ, a 93% reduction in cercarial penetration was seen at 0 hr and a 98%+ reduction rate was seen from 4 to 24 hr postexposure. However, Cremophor El alone had an essentially equivalent effect on cercarial penetration from 8 to 92 hr after administration. These unexpected results led us to investigate both castor oil and ricinoleic acid (castor oil is 87% ricinoleate as triglyceride) as oral anti-penetration agents. Mice were given the lipids orally by gavage for 7 days. On Day 8, each group of 12 mice was exposed to approximately 75 75Se-radiolabeled cercariae. Castor oil gave protection rate ranging from 90 to almost 100% at an optimal concentration of 0.3 ml/day x 3 or 7 days (approximately 9.8 g/kg/day). These observations suggest that chemoprophylaxis may be possible by dietary supplementation with lipids having anti-penetration activity or by molecules that resemble these lipids.

Administration, Oral

Transcriptional regulation of a promoter in the men gene cluster of Bacillus subtilis.

The control of men gene expression during growth and sporulation of Bacillus subtilis was examined at the transcriptional level. Two different approaches were used. (i) Steady-state levels of men-specific mRNA were measured directly. (ii) A men'-lacZ gene fusion was constructed. In both cases, it was observed that men promoter activity was maximal at the onset of sporulation and declined soon thereafter. These kinetics were similar to the pattern of menaquinone accumulation previously observed. Expression from the men promoter was independent of the presence of the products of the spo0A and spo0H genes and was enhanced by addition of glucose and glutamine to the culture medium. DNA sequence analysis of the promoter region revealed a potential recognition site for the principal vegetative form of RNA polymerase but not for any of the known minor polymerase forms. The functionality in vivo of the promoter sequence was confirmed by high-resolution S1 nuclease mapping of the transcript start site. An additional sequence element was identified that is shared by the sdhA, citG, and ctaA promoters and may indicate a common regulatory mechanism in the expression of these genes.

Bacillus subtilis

Arterial vasodilator, systemic and coronary hemodynamic effects of nisoldipine in congestive heart failure secondary to ischemic or dilated cardiomyopathy.

The systemic and coronary hemodynamic and neurohumoral effects of nisoldipine, a calcium antagonist drug with high vascular specificity, were investigated in 17 patients with chronic congestive heart failure (CHF). Brachial artery infusions (n = 9) decreased forearm vascular resistance in a dose-dependent manner, attesting to its powerful arterial vasodilator properties. A dose of 3 micrograms/kg intravenously decreased mean blood pressure 16% and systemic vascular resistance 33%, while increasing stroke index 19% and ejection fraction 21% at rest and similarly during exercise. Pulmonary capillary wedge pressure decreased significantly during exercise. Intravenous infusion of nisoldipine increased rest coronary sinus flow 10% (p less than 0.05, n = 7), decreased rest and exercise coronary vascular resistance 28% and 19% (p less than 0.01) and rest myocardial oxygen consumption 14% (p less than 0.05). In 13 patients similar systemic hemodynamic results were found after treatment with oral nisoldipine, 2 X 20 mg for 4 weeks. Stroke index and stroke work index increased long-term more than acutely (31% and 12.4% vs 19% and 4.5% at rest, both p less than 0.05), which may indicate a compensated mild cardiodepressant effect of intravenous nisoldipine. Changes in forearm vascular resistance after intra-arterial administration did not correlate with changes of systemic vascular resistance after intravenous administration, suggesting that factors other than vascular calcium entry blockade importantly influence hemodynamic responses. Elevated control plasmas norepinephrine and renin levels, on average, did not change during chronic therapy but individual changes were compatible with a reduction of sympathetic activity in patients with hemodynamic improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

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