Analysis of molecular variance (AMOVA) of Y-chromosome-specific microsatellites in two closely related human populations [published erratum appears in Hum Mol Genet 1997 May;6(5):828]

The analysis of seven Y-chromosome-specific microsatellite loci revealed a high level of polymorphism in two closely related human populations (Dutch, n = 89, and German, n = 70). Four of these loci were found to generate at least 77 different haplotypes, only 15 of which were shared by the two populations. These results demonstrate that highly informative PCR-based DNA typing of the Y chromosome is now feasible. Assuming a stepwise mutation model, a network comprising all minimum spanning evolutionary trees connecting the haplotypes was constructed. Analysis of molecular variance based upon this network indicated that the within-population heterogeneity with respect to haplotype descent was significantly smaller than the between-population heterogeneity, suggesting that males were more closely related to males from their own population as opposed to males from the other population. These findings suggest that Y-chromosomal microsatellites might be very useful not only for forensic purposes but also in association studies of multifactorial traits, allowing the characterization of the level of genetic distinctiveness of supposedly inbred or isolated populations and discrimination even between closely related populations.      

The regional registry of gastro-intestinal cancer North Baden (2.2 million inhabitants)

Summary The advantages of a population-based registry are discussed. It is shown that a registry for gastro-intestinal cancer in a district with expert medical care based upon histo-pathological diagnosis, has the principal advantage that it limits the sites of material collection to a few effective contributors, thus providing highly accurate data. The disadvantage of collecting data by two separate steps should be tolerated. The geographic situation and the organization of the regional registry for gastro-intestinal cancer in North Baden are described and the incidences for these cancers for the years 1971–1975 are given for the population of 2.2 million.Supported by the DFG (SFB 136)     

Mechanism of imipenem resistance acquired by threePseudomonas aeruginosa strains during imipenem therapy

Imipenem sensitive pretherapy isolates (MICs 1–2 mg/l) and the corresponding resistant posttherapy isolates (MICs 16 mg/l) ofPseudomonas aeruginosa from three patients undergoing imipenem treatment were analyzed to establish the resistance mechanism. The identity of pyocin types, serotypes, DNA restriction endonuclease profiles and plasmid profiles strongly suggested isogenicity of pre- and posttherapy isolates. The imipenem resistant posttherapy isolates showed cross-resistance only to another carbapenem, meropenem. There were neither qualitative nor quantitative differences between pre- and posttherapy isolates in -lactamase production. Affinity of the penicillin-binding proteins 1A, 1B, 2, 3, 4, 4 and 5 for [¹⁴C]imipenem was the same in pre- and posttherapy isolates. One-dimensional and two-dimensional gel electrophoresis of outer membrane protein preparations showed diminished expression of an outer membrane protein of about 46.5 and 47.5 kilodaltons, respectively, in the posttherapy isolates. This protein had an apparent isoelectric point of about pH 5.2 in two-dimensional gel electrophoresis. Growth in proteose peptone no. 2 broth did not reduce expression of this outer membrane protein, which spoke against its identity with the outer membrane protein D1. The permeability of the outer membrane for imipenem was reduced in the posttherapy isolates, since addition of 0.5 or 0.25 of the MIC of the permeabilizing agent ethylenediaminetetraacetate reduced the MICs of imipenem for all isolates from each patient to the same (susceptible) level. The diminished expression of one of the outer membrane proteins might be the reason for this reduced permeability.     

Disease type-associated increases of the plasma levels and ligand expression for natural alpha- or beta-galactoside-binding immunoglobulin G subfractions in patients with lung cancer

The presence of natural carbohydrate-binding antibodies may play a role in host defence against malignant cells in addition to elicitation of an immune response by artificial carbohydrate antigens. Human serum contains immunoglobulin G(2) (IgG) fractions with selectivity to alpha- and to beta-galactosides, respectively, irrespective of the type of blood group of the donor. To determine whether these naturally occurring subfractions may have any relevance for tumor disease control, their binding to malignant cells was ascertained by cytofluorimetric assays in vitro with a number of human tumor cell lines of different histogenetic origin. The affinity of cell binding was comparable to that of binding to lactosylated or melibiosylated neoglycoconjugates as model ligands in solid-phase assays and K-D values were found to be in the range of 5-300 nM. Cross-reactivity of the anomer-selective subfractions to the other type of ligand was observed to be rather low. When the IgG contents of plasma samples of patients with diverse types of lung cancer were assessed, the concentrations of both galactoside-binding immunoglobulin G subfractions were significantly increased in association with presence of small cell lung carcinoma and of metastatic lesions to the lung without any marked change in the overall IgG plasma level. Such an apparently general enhancement was seen for patients with adenocarcinoma and included both subfractions with no impact on their percentage in the total IEC content. When detergent extracts of tumor and tumor-free specimens of the same patient were analyzed with the affinity purified antibody subfractions to comparatively determine ligand presentation, increases in sugar-inhibitable binding were especially noted for the tumor tissue of small cell lung carcinomas and apparently tumor-free samples of cases with lung metastasis. Material from other types of lung cancer revealed no significant indication for disease-related alterations with the exception of carcinoids. These data demonstrate that plasma levels and ligand expression for two types of natural galactoside-binding immunoglobulin G fractions can show nonuniform responses in patients within the class of lung cancer. They encourage to deliberately monitor these parameters of the natural carbohydrate-directed antibody fractions in cancer patients with various types of disease to clarify the clinical significance of respective malignancy-associated changes.     

Bilateral and simultaneous quadriceps tendon rupture in secondary hyperparathyroidism. A case report

A case of bilateral simultaneous rupture of the quadriceps tendon without significant trauma is presented. Generally there is an association with chronic metabolic disorders, such as chronic renal failure and secondary hyperparathyreoidism, as well as hormonal diseases. The ruptures appeared in a 34-year-old man with chronic renal failure and severe secondary hyperparathyreoidism. Etiology, diagnostic procedures and treatment in comparison with the international literature are described. We discuss the value of ultrasound screening as a diagnostical and follow-up tool.     

Prognostic relevance of detection of ligands for vertebrate galectins and a Lewis(Y)-specific monoclonal antibody

Tissue sections taken from 157 potentially curatively operated lung carcinoma patients (70 epidermoid carcinomas, 68 adenocarcinomas, 15 large cell anaplastic, and 4 small cell anaplastic carcinomas) were examined by a standardized histochemical protocol in a prospective study evaluating the extent of various types of probes to serve as prognostic indicators in lung cancer. Detailed clinical records and survival data (minimum 56 weeks, maximum 96 weeks) were correlated to the results of the histochemical reactions. The study centres on monitoring the expression of galactoside-containing epitopes in tumor cells by human, animal and plant lectins: and with a monoclonal antibody. In addition, affinity-purified subfractions of natural antibodies from human serum with preferential affinity to alpha- and beta-galactosides, respectively, were employed. Significant contributions to the estimation of the survival of patients are given by clinical parameters (pT, pN stage), number of resected and positive lymph nodes and presence of tumor metastases into specific lymph nodes (No. 5 and No. 6 right and left). With respect to the relevance of subsets of beta-galactosides, the galectin from chicken liver (CL-16) and the Le(y)-specific monoclonal antibody unveiled a negative correlation at a statistically significant level. The predictive value of binding of the animal lectin CL-16 was especially pronounced for patients with advanced tumor stages, pointing to a potential role of such lectin-reactive beta-galactosides in late tumor stages or progression.     

Alpha-motoneuron excitability at high altitude

Summary It has been hypothesized that chronic hypobaric hypoxia could lead to inhibition of the-motoneuron pool, thus limiting the maximal activation of working skeletal muscles. To test this hypothesis six subjects [32 (SEM 2) years] were evaluated in resting conditions, at sea level and after acclimatization at 5,050 m. The recruitment curves of the Hofmann-reflex (H-) and the direct muscle-response (M-) of the right soleus muscle were obtained by stimulating the posterior tibeal nerve with different intensities while recording the electromyogram of the soleus muscle. From the recorded data the net-motoneuron excitability (ratio of maximal H-reflex to M-response H_max : M_max ratio), the threshold and gain for both responses, obtained from linear regressions through the rising phase of the recruitment curves of both responses, as well as the latency times of both responses were determined. The latency times and the H_max :M_max ratio were unchanged at altitude. The thresholds of both responses and the gain of the M-response were unaltered. The gain of the H-response was significantly higher at altitude when compared to sea level. It is concluded that in the acclimatized subjects at rest the signal conduction velocity through the different parts of both pathways was unaltered and therefore nerve and muscle conduction velocity as well as synaptic and muscle end-plate transmission were unchanged, that the recruitment of the H-reflex was slightly facilitated after acclimatization to high altitude suggesting increased excitability of the-motoneurons, through either postsynaptic facilitatory changes in the soma or a different descending drive, and that the unchanged H_max:M_max ratio indicated no change in the net excitatory and inhibitory influences on the-motoneuron pool. The above hypothesis is thus not strengthened by the results that were, however, obtained in resting conditions.     

Long distance image transfer: first results of its use in histopathological diagnosis.

Histopathological images were transferred by use of normal telephone lines between three pathology institutes located in three different cities in the FRG. Images were digitized using a colour TV camera and stored in a special computerized image transmission system. The stored image was transferred and visualized on a (receiver) colour TV screen after dialing the telephone number connected to the receiver image transmission system. An additional telephone dialogue was activated by use of a normal acoustic telephone, and the diagnostic difficulties of the underlying image were discussed. Diagnostic assistance was possible in all transferred cases as well as histopathological diagnosis. Resolution of the images was set at 512 x 512 pixel x 8 bit. Image transfer time was 3.2 min on average. The differences between the original and transferred image were measured by "retransfer" of the original image and by subtracting the two images from each other. No major transfer errors could be measured.     

Nachweis von pharmakologisch aktiven Substanzen im Pfortaderblut von Hunden bei Verschluß der Arteria mesenterica superior

Zusammenfassung Bei Hunden mit experimentellem Verschluß der Arteria mesenterica superior kommt es zu einem deutlichen Anstieg der Serotonin-, Kinin-und Katecholaminkonzentrationen im Pfortaderblut, zu einem Anstieg der Prostaglandin F₂-Konzentration, aber nur unmittelbar nach Anlegen oder Wiedereröffnung des Verschlusses.Unsere experimentellen Ergebnisse machen es unwahrscheinlich, daß diese genannten Substanzen für die Entwicklung von Erosionen oder Ulcera, wie sie nach Verschluß der Arteria mesenterica superior beobachtet werden, ursächlich verantwortlich sind, da diese pharmakologisch aktiven Substanzen letztlich zu geringe Konzentrationserhöhungen erfahren. Andererseits ist eine mögliche additive Wirkung dieser unterschwelligen Konzentration von Serotonin, Kinin und Katecholamin nicht mit Sicherheit auszuschließen.

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The demonstration of pharmacological active substances in the portal vein blood of dogs after occlusion of the superior mesenteric artery

Summary The experimental occlusion of the superior mesenteric artery in dogs is followed by a significant rise of serotonin-, kinin- and katecholamin-concentrations in the portal vein blood. The rise of the prostaglandin-F₂-concentration occurred only immediately after the occlusion or reopening of the occluded superior mesenteric artery.Under our experimental conditions the measured concentrations of these substances in the portal vein blood are too low and ineffective for the development of peptic erosions in the stomach as observed after occlusion of the superior mesenteric artery. On the other hand a possible additiv effect of the underswelling concentrations in these different substances cannot be excluded.