Bilateral radiotherapy in cases of one-sided choroidal metastases.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
S Hoffmann
Publications and source records attributed to S Hoffmann.
Structure-affinity studies of C-terminally modified analogs of neuropeptide Y led to a novel class of peptidic Y1 receptor antagonist.
A novel type of C-terminally modified analogs of the 36-mer peptide hormone neuropeptide Y has been synthesized, characterized and tested with respect to receptor affinity and biological activity in various systems. The compounds were obtained by synthesizing the fully protected peptide fragment NPY 1-35 or analogs of this, and coupling it in solution to various amines, alcohols, and modified tyrosine residues. It could be confirmed, that the C-terminal tyrosineamide of NPY is essential for its affinity to the Y1 receptor subtype. Obviously, the amino group of the amide part is more important than the oxygene atom of the carbonyl group, as NPY 1-35-tyrosinol has a lower affinity than NPY 1-35-tyrosinethioamide. NPY 1-35-tyramide could be shown to act as an antagonist in a Ca2+ release assay in human neuroblastoma cells. Analogs of NPY 1-35-tyramide showed the same structure-affinity relationships as NPY itself, suggesting, that there exists the same binding mode for the agonist and the antagonist.
Amino Acid Sequence↗
Hepatitis B core antibody screening in a high prevalence group: comparison of three enzyme immunoassays using receiver operating characteristic analysis.
Selected sera from 296 homosexual men were screened by 3 commercially available anti-HBc enzyme immunoassays (EIA). All patients could be classified either as non-immune to hepatitis B, or with current or previous hepatitis B infection. Using the cut-off optical density values (O.D. values) recommended by the respective manufacturers, the results from these three assays were identical for 83% of the serum samples. For anti-HBc reactivity, the ratio (percentage) was calculated using O.D. sample x 100 divided by the O.D. cut-off value. Employing these ratios, sensitivities and specificities for the three assays were compared. All assays performed well when analyzed by receiver operating characteristic curves with area under the curves of 96-97%. A higher specificity, with only a marginal loss of sensitivity could be achieved by lowering the cut-off to 55% for the Enzygost EIA, to 85% for the Enzygost-monoclonal EIA and to 60% for the Corzyme EIA. Using the modified cut-off values, the results with the three assays agreed for 93% of the serum samples.
Hepatitis Antibodies↗
[Percutaneous catheter drainage of an unusually extensive tuberculous hypostatic abscess].
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Adult↗
Shewanella alga bacteremia in two patients with lower leg ulcers.
The first Danish cases of Shewanella alga bacteremia in two patients with chronic lower leg ulcers are reported. Both patients were admitted to the hospital during the same month of a very warm summer and had been exposed to the same marine environment, thereby suggesting the same source of infection. Both patients survived; however, one of them had extensive myonecrosis, while the other patient had an uncomplicated course. The strains were initially believed to be Shewanella putrefaciens on the basis of key characteristics and results of the API 20NE identification system (bioMérieux, Marcy l'Etoile, France), but further genetic and physiological analyses identified them as Shewanella alga.
Aged↗
Potential diagnostic value of sampling oral mucosal surfaces for Actinobacillus actinomycetemcomitans in young adults.
Actinobacillus actinomycetemcomitans has been implicated in the pathogenesis of several forms of early onset and refractory adult periodontitis. Early diagnosis of colonization of the oral cavity might be of importance in order to initiate preventive measures. The aim of the present study was to determine the potential diagnostic value of oral mucosal and salivary tests to identify, among healthy young men with no or minor periodontal disease, individuals colonized by A. actinomycetemcomitans. Two hundred and one male recruits, 18-25 yr of age, took part in the present study. Mean values of periodontal parameters suggested only minor periodontal disease. Of the sites, 64.8 +/- 17.6% (mean +/- SD) had a periodontal probing depth (PPD) of 1 or 2 mm, only 1.6 +/- 2.9% deep sites of > or = 5 mm were detected. More than 1000 subgingival and extracrevicular samples were selectively cultivated for A. actinomycetemcomitans. The organism was isolated in 55 subjects (27%). The odds for presence of at least 1 deep site of 5 mm was increased by a factor 1.99 if A. actinomycetemcomitans, could be recovered. In identifying subjects colonized by A. actinomycetemcomitans, diagnostic test parameters sensitivity and predictive value for a negative test were 74.5 +/- 5.9% and 91.1 +/- 2.3%, respectively, for both saliva and dorsum of tongue samples. In contrast, pooled subgingival plaque from mesial surfaces of 1st molars was only 34.5 +/- 6.4% sensitive; the negative predictive value was 80.2 +/- 3.0%. The results point to a high diagnostic value of oral mucosal and especially saliva samples to identify young adult individuals colonized by A. actinomycetemcomitans.
Adolescent↗
Natural distribution of oral Actinobacillus actinomycetemcomitans in young men with minimal periodontal disease.
A total of 1005 subgingival and extracrevicular samples from 201 male recruits, 18-25 yr old, were selectively cultivated for Actinobacillus actinomycetemcomitans. The organism was isolated in 55 subjects (27%); 9.5% of pooled subgingival plaque samples from first molars, 14% cheek mucosa, 20% dorsum of tongue and 20% saliva samples were culture-positive. In order to divide the study population into distinct clinical categories, cluster analysis was performed, based on previous caries experience, probing pocket depth categories, bleeding scores, visible plaque and calculus. Two clusters (n = 86 and n = 92, respectively) were identified with no or minimal periodontal disease (mean +/- standard deviation % of periodontal probing depth 1-2 mm 78.7 +/- 10.4% and 57.4 +/- 12.6%, respectively; virtually no periodontal probing/depth in excess of 4 mm) and a relatively low DMF-S (22 +/- 13). A third cluster (n = 22) had, in contrast, a high DMF-S (47.7 +/- 17.2) and a relatively high % of periodontal pockets of > or = 5 mm (5.9 +/- 5.2%). Prevalence of A. actinomycetemcomitans in this cluster was 41%, while the organism was found in 23% and 27% in the minimally diseased populations (p < 0.15). Whereas no heterogeneity of associations between subgingival and extracrevicular occurrence of the organism could be ascertained in different clusters, the organism was significantly more often identified in extracrevicular material, especially dorsum of tongue samples, compared with subgingival plaque (McNemar's chi2 = 12.45, p < 0.001). Multiple linear regression analysis revealed the number of A. actinomycetemcomitans positive samples as well as the % of sites bleeding on probing being positively associated with the % of sites with a probing pocket depth of > or = 5 mm (R2 = 0.345, p < 0.0001). The present large-scale investigation points to the wide distribution of this putative periodontopathogen in young individuals with minimal periodontal disease.
Adolescent↗
The pef fimbrial operon of Salmonella typhimurium mediates adhesion to murine small intestine and is necessary for fluid accumulation in the infant mouse.
We investigated the role of the pef operon, containing the genes for plasmid-encoded (PE) fimbriae of Salmonella typhimurium, in adhesion to the murine small intestine. In an organ culture model, a mutant of S. typhimurium carrying a tetracycline resistance cassette inserted in pefC was found to be associated in lower numbers with murine small intestine than the wild-type. Similarly, heterologous expression of PE fimbriae in Escherichia coli increased the bacterial numbers recovered from the intestine in the organ culture model. Adhesion to villous intestine mediated by PE fimbriae was further demonstrated by binding of an E. coli strain expressing PE fimbriae to thin sections of mouse small intestine. The contribution of pef-mediated adhesion on fluid accumulation was investigated in infant mice. Intragastric injection of S. typhimurium 14028 and SR-11 caused fluid accumulation in infant mice. In contrast, pefC mutants of S. typhimurium 14028 and SR-11 were negative in the infant mouse assay. Introduction of a plasmid containing pefBACD and orf5, the first five genes of the pef operon, into the pefC mutant complemented for fluid accumulation in the infant mouse assay. However, heterologous expression of PE fimbriae in E. coli did not result in fluid accumulation in the infant mouse, suggesting that factors other than fimbriae are involved in causing fluid accumulation.
Animals↗
The enhancer domain of the human cytomegalovirus major immediate-early promoter determines cell type-specific expression in transgenic mice.
The human cytomegalovirus (HCMV) major immediate-early promoter (MIEP) is one of the first promoters to activate upon infection. To examine HCMV MIEP tissue-specific expression, transgenic mice were established containing the lacZ gene regulated by the MIEP (nucleotides -670 to +54). In the transgenic mice, lacZ expression was demonstrated in 19 of 29 tissues tested by histochemical and immunochemical analyses. These tissues included brain, eye, spinal cord, esophagus, stomach, pancreas, kidney, bladder, testis, ovary, spleen, salivary gland, thymus, bone marrow, skin, cartilage, and cardiac, striated and smooth muscles. Although expression was observed in multiple organs, promoter activity was restricted to specific cell types. The cell types which demonstrated HCMV MIEP expression included retinal cells of the eye, ductile cells of the salivary gland, exocrine cells of the pancreas, mucosal cells of the stomach and intestine, neuronal cells of the brain, muscle fibers, thecal cells of the corpus luteum, and Leydig and sperm cells of the testis. These observations indicate that the HCMV MIEP is not a pan-specific promoter and that the majority of expressing tissues correlate with tissues naturally infected by the virus in the human host.
Animals↗
Developmental analysis of the cytomegalovirus enhancer in transgenic animals.
The major immediate-early promoter (MIEP) of human, cytomegalovirus (HCMV) constitutes a primary genetic switch for viral activation. In this study, regulation of the enhancer-containing segment (nucleotides -670 to +54) of the HCMV MIEP attached to the 1acZ reporter gene was examined in the developing embryos of transgenic mice to identify temporal and tissue-specific expression. We find that the transgene reporter is first detected as a dorsal stripe of expression in the neural folds of embryos at day 8.5 postcoitum (p.c.). A broad expression pattern is exhibited in embryos at day 9.5 p.c. This pattern becomes more restricted by day 10.5 p.c. as organogenesis progresses. By day 14.5 p.c., prominent expression is observed in a subpopulation of central nervous system cells and spinal ganglia, endothelial cells, muscle, skin, thyroid, parathyroid, kidney, lung, liver, and gut cells, and the pancreas and submandibular and pituitary glands. This distribution pattern is discussed in relation to human congenital HCMV infection. These results suggest that the transcriptional activity of the HCMV MIEP may determine in part, the ability of the virus to specifically target developing fetal tissues in utero.
Animals↗
Angiotensin I converting enzyme and chymase in cardiovascular tissues.
Recent studies have provided evidence that the human cardiovascular tissues contain components of the renin-angiotensin system: angiotensinogen, renin, angiotensin I converting enzyme (ACE), chymase and angiotensin II (Ang II) receptors. In addition to ACE, a cardiac Ang II forming serine proteinase, human heart chymase, has been identified in the human left ventricle. Unlike rat heart, only a minor (approximately 11%) component of Ang II forming activity in the human left ventricle was due to ACE, since the majority (approximately 80%) of activity was due to chymase. Human heart chymase has been purified to homogeneity and characterized. Recently, the cDNA and gene for this enzyme have been cloned. Biochemical characterization revealed that heart chymase is the most efficient and specific Ang II forming enzyme described thus far. The different cellular and regional distribution of ACE and heart chymase in the heart as well as in blood vessels implies distinct pathophysiological roles for these two Ang II forming enzymes. Several reports indicate that ACE-independent Ang II formation appears to take place in hypoxic or ischemic heart or blood vessel in vivo and to be involved in vascular remodeling after balloon injury. Therefore, it is very important to clarify the detailed mechanisms of the tissue Ang II formation in humans and its contribution to the pathophysiological changes in cardiovascular disease. In this review, we review the pathophysiological roles of the two main Ang II forming enzymes, ACE and chymase, in cardiovascular homeostasis.
Animals↗
Antibiotics for sore throats. Potential of antigen detection tests.
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Anti-Bacterial Agents↗
Frozen shoulder--treatment and results.
Even today the aetiology of the frozen shoulder is still under discussion. At the Orthopaedic Department of the Medizinische Hochschule Hannover, 118 persons with a frozen shoulder were treated as in- or outpatients between 1980 and 1988. We investigated the results of two different specific therapy concepts. Most of the patients received a mixture of drug therapy and physical rehabilitation under the guidance of a physiotherapist. In a smaller group of patients, the frozen shoulder was mobilized under anaesthesia (mobilisation force). After an average follow-up time of 3.8 years from the start of treatment, 93% of the patients was examined by means of an individual subjective rating (score). In addition, a clinical examination was performed in 69% of the cases. According to the subjective personal rating (score) as well as the improvement in range of motion, moderate mobilisation led to better results than the mobilisation under anaesthesia.
Adult↗
[Blood relationship].
In every-day medical practice, blood relationship of spouses hardly ever play an important part. Mainly for genetic counselors and pediatricians the question of consanguinity of a child's parents arises when either a rare, often hereditary, disorder is diagnosed for the first time in a family, or potential parents want information on the risk for hereditary diseases. A probability calculus based on the corresponding hereditary factors of the joint ancestors establishes how likely homozygotes for hereditary diseases among the offspring of [blood]-related spouses - often cousins of the first or second degree - is. Furthermore, proof of the parents' consanguinity may explain a child's unexpected hereditary disease [especially autosomal recessive disorders] and, at the same time, it means a higher risk of repetition for the affected child's desired siblings. Incest represents a special form of genetic risk; this question arises either in connection with the adoption of a child, which was conceived by an incestuous couple, or with such a child's own family planning later on. Even the parents' descent from an ethnically, politically, religiously or linguistically isolated background may gave a similar impact on the appearance of hereditary disorders: an accumulation of rare genes has to be taken into account; factors causing disorders have to be expected among these genes, too. In the following, all major aspects of the situations described above will be given in detail.
Consanguinity↗
[Diagnosis of sore throat. A multipractice study of 3 different ways of antigenic determination for detection of group A streptococci in throat swabs].
During five months in the winter of 1992/1993, 34 general practitioners (GPs) from 18 offices participated in a clinical testing of three group A streptococcal antigen detection test (ADT) kits (Abbott TestPack Strep A Plus (Abbott), Concise Strep A, Hybritech (Concise) and Kodak SureCell Strep A (Kodak)). The GPs obtained duplicate throat swabs, one for processing with the ADT kit, the other for culture reference at The Streptococcus Laboratory (Bacteriological Department, Statens Seruminstitut, Copenhagen). A total of 1389 patients were enrolled in the study, thirty percent of whom were infected by group A streptococci. The following results were obtained: Abbott: Sensitivity: 76%, specificity: 99%, positive predictive value: 97%, negative predictive value: 91%. Concise: Sensitivity: 82%, specificity: 95%, positive predictive value: 86%, negative predictive value: 92%. Kodak: Sensitivity: 84%, specificity: 87%, positive predictive value: 73%, negative predictive value: 93%. As a follow-up to the main study, each GP filled in a questionnaire, stating his opinion about the investigated ADT kit. Considering the practical handiness, Concise scored higher than Abbott, which in turn scored higher than Kodak. In conclusion, Abbott and Concise are recommended for the diagnosis of group A streptococcal pharyngotonsillitis in general practice.
Antigens, Bacterial↗
[Course and prognosis of subacute cutaneous lupus erythematosus. A prospective study of 34 patients].
34 patients with subacute cutaneous lupus erythematosus (SCLE) were prospectively followed up and examined twice in 1986-1989 and 1990-1991, with a minimal interval of 2 years. The findings obtained were documented in a computerized registry and were evaluated by computer-assisted analysis. Thirty-one women and three men aged 23-66 years at the time of the first documentation (FD) were included in the study. The disease had lasted an average 6.5 years (from a few months to 39 years). Prominent cutaneous manifestations of SCLE were shown by 79.4% of the patients at the first visit compared to 58.8% at the second documentation (SD), whereas the incidence of acrolocalized vasculitis increased (FD 20.6%, SD 41.2%), as did that of Raynaud phenomenon (FD 20.6%, SD 26.5%). Mild extracutaneous symptomatology was found in 70.6% (FD) and in 85.3% (SD) of the SCLE patients. Arthralgia (FD 47%, SD 61.8%) and symptoms suggesting some involvement of the peripheral or central nervous system (FD 29.4%, SD 50%) were noted most frequently. Overall, during the follow-up there was a quantitative mild increase of extracutaneous symptomatology; a significant correlation between the presence of acrolocalized vasculitis and arthralgia was found. In conclusion, the prognosis of SCLE appears rather benign; fulminant courses were not observed. However, the risk of mild systemic involvement clearly increases during the prospective course of the disease, whereby acrolocalized vasculitis can be regarded as a cutaneous marker for extracutaneous manifestations.
Acrodermatitis↗
Tissue angiotensin II system in the human heart.
Several intervention studies with angiotensin I converting enzyme (ACE) inhibitors have demonstrated a remarkable improvement in the treatment of patients with primary hypertension and congestive heart failure. Since ACE inhibitor therapy in patients with congestive heart failure not only improves systemic haemodynamics but also provides a better prognosis, the cardiac renin-angiotensin system is apparently one of the major targets of ACE inhibitor therapy. Recent studies provided evidence that the human heart contains high affinity Ang II (Ang II) receptors with both subtype population and ACE. In addition to ACE, a novel cardiac Ang II forming enzyme (human chymase) has been identified in human hearts. Unlike in the rat heart, the minor (10%) component of Ang II-forming activity in the left ventricle is due to ACE, whereas the major (80%) component is due to human chymase. This novel cardiac serine proteinase has been purified from the human left ventricle and characterized, and recently, the cDNA and the gene for this enzyme have been cloned. Biochemical characterization revealed that human chymase is the most efficient and specific Ang II-forming enzyme described thus far, but the cellular and regional distribution of the two Ang II-forming enzymes seems to be different. ACE is mainly localized in endothelial cells and fibroblasts and the expression level is higher in atria than ventricles, whereas chymase is synthesized and stored in secretory granules of mast cells, endothelial cells, and mesenchymal cells, and after its secretion localized in the interstitial region of the myocardium and its expression is higher in ventricles than atria. These results imply distinct roles of these two Ang II-forming enzymes in cardiac Ang II formation and in the physiological function of the human heart. Since localization of cardiac renin and angiotensinogen were also identified in human heart, it is important to understand the detailed mechanisms of the tissue Ang II formation and its contribution to the pathophysiological changes in cardiovascular diseases.
Angiotensin II↗
Lautropia mirabilis gen. nov., sp. nov., a gram-negative motile coccus with unusual morphology isolated from the human mouth.
An organism that seems to be identical to Orskov's 'Sarcina mirabilis' [Orskov, J. (1930) Acta Pathol Microbiol Scand Suppl III, 519-541] has been rediscovered in specimens from the upper respiratory tract of humans. Six strains were studied, and the results, which conformed to Orskov's description of S. mirabilis, were as follows. Rough to smooth colonies grow on many plated media and show extremely polymorphic cell morphology with round cells with diameters from 1 to > 10 microns. The smallest cells were often motile with circular movements. Strains were Gram-negative, facultatively anaerobic, oxidase and urease positive, and weakly catalase positive. Nitrate and nitrite were reduced, and glucose, fructose, sucrose and mannitol were fermented. Polysaccharide was produced on sucrose agar. Electron microscopy showed coccoid cells with a bundle of three to nine flagella, a Gram-negative cell-wall morphology, and aggregates of irregular cells held together by a common surface layer. The mean mol% (G+C) of the organisms was 65.0. 16S-ribosomal RNA sequencing revealed that the organism belongs to the beta subgroup of Proteobacteria, separate from all other described genera, but most closely related to Burkholderia. The name Lautropia mirabilis is proposed for this organism.
Bacterial Typing Techniques↗