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Biomedical subjects

J Koch

Publications and source records attributed to J Koch.

At least 199 records · Page 11Linked to original sources

Murine models for evaluating antiretroviral therapy.

The pandemic of the acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus type 1 (HIV-1), requires rapid development of effective therapy and prevention. Analysis of candidate anti-HIV-1 drugs in animals is problematic since no ideal animal model for HIV-1 infection and disease exists. For many reasons, including small size, availability of inbred strains, immunological reagents, and lymphokines, murine systems have been used for in vivo analysis of antiretroviral agents. Here we review currently available murine models involving HIV-1 in transgenic mice and in chimeric mice reconstituted with human cells, as well as murine systems using retroviruses of the subfamily Oncovirinae rather than Lentivirinae. We report our results on various antiretroviral treatment strategies, including chemoprophylaxis after acute retroviral exposure, therapy of chronic viremia, quantitative analysis of combination therapy, and therapy during pregnancy and in the neonatal period aimed at preventing viremia in the offspring. Due to our highly effective postexposure treatment protocols with 3'-azido-3'-deoxythymidine (zidovudine) combined with recombinant human interferon-alpha A/D, retrovirus-inoculated mice developed immunity to the virus to which they were exposed, which will allow us to determine the nature of protective antiretroviral immunity in inbred mice.

Animals↗

cpc-2, a new locus involved in general control of amino acid synthetic enzymes in Neurospora crassa.

In Neurospora crassa starvation for single amino acids leads to derepression of enzymes in many amino acid synthetic pathways. Regulation occurs at the level of transcription via "general amino acid (or cross-pathway) control". In this paper a new regulatory gene, cpc-2, is described that specifies a positive, trans-acting effector involved in this control. This gene, located on linkage group VII, was identified by a recessive mutation, U142, which results in sensitivity for two amino acid analogues and a lack of enzyme derepression in response to amino acid limitation. It was shown that cpc-2 (U142) impairs the activation of transcription of amino acid structural genes in several biosyntheses. The only other known regulatory gene involved in general amino acid control of Neurospora is cpc-1. Transcription of the cpc-1 gene, however, is increased in response to amino acid starvation irrespective of the presence of the mutation U142.

Amino Acids↗

Intestinal infusion of a liquid diet alters CCK and NPY concentrations in specific brain areas of rats.

Cholecystokinin (CCK) and neuropeptide Y (NPY) have been implicated in the control of food intake in a number of species. This study was carried out to determine 1) whether nutrient-related stimulation of the upper small intestine could activate central CCK and NPY neuronal systems, resulting in changes in concentration of these peptides in specific brain areas, and 2) the influence of the circadian cycle on nutrient-related effects. Four groups of rats received treatments of either 1.0 ml saline (S) or Ensure liquid diet (E) infused into the duodenum either during the dark (D) or light (L) phase of the circadian cycle. CCK and NPY concentrations in extracts of specific brain areas were measured by RIAs. CCK concentration in the supraoptic n. (SON) was higher in D than in L, regardless of infusion treatment, and in the dorsal parabrachial n. area (DPN), CCK concentration was higher in E than S infused rats, regardless of circadian phase. CCK concentration in the dorsal motor vagal n. area (DMV) was higher in E, but only during L. NPY concentration was higher in DPN and paraventricular n. areas (PVN) and lower in the suprachiasmatic n. area (SC) after E, regardless of circadian phase. The changes in concentration of CCK and NPY in specific brain areas in response to food in the upper intestine suggest that nutrient-related signals from the intestine can activate specific CNS CCK and NPY-containing neural pathways.

Animals↗

A case of 46,XX,r(X) (p1q1) diagnosed by in situ hybridization.

A small marker chromosome was identified as an X-derived ring chromosome by in situ hybridization with a biotinylated X-chromosome specific a-satellite DNA probe. This procedure clearly determined the chromosomal origin of the marker chromosome, which had been impossible to define by conventional cytogenetic techniques including high resolution banding.

Centromere↗

Formation of a minichromosome by excision of the proximal region of 17q in a patient with von Recklinghausen neurofibromatosis.

An interstitial deletion, 17cen----q11.2 (or q12), and a small extra chromosome was found in a sporadic case of von Recklinghausen neurofibromatosis (NF1). In situ hybridization with a chromosome 17-specific alpha-satellite probe showed that the small chromosome was derived from the deleted region, most likely by an excision/ring formation. This chromosome rearrangement is in agreement with the localization of the von Recklinghausen neurofibromatosis (NF1) locus to the proximal region of 17q, but with a more distal breakpoint than observed in two previously described reciprocal translocations associated with NF1. If the NF1 gene has been truncated by the present rearrangement, it may suggest that the NF1 gene is a very large gene at the genomic level. Alternatively, NF1 in this patient may be caused by the gradual loss in somatic cells of the small chromosome carrying an intact NF1 gene, thereby suggesting a recessive mechanism at the gene level. Finally, an intact NF1 gene may have been placed in close proximity with alpha-satellite sequences, which might cause inactivation of the gene. The small supernumerary chromosome may not only facilitate the cloning of the NF1 gene itself, but also offers explanations of the mechanism underlying development of the disease.

Chromosome Aberrations↗

Detection of point mutations in amplified single copy genes by biotin-labelled oligonucleotides: diagnosis of variants of alpha-1-antitrypsin.

Specific analysis for point mutations in genomic DNA has until recently been a difficult and time-consuming task, using large amounts of unstable, hazardous and expensive 32P. By enzymatically amplifying the mutation-bearing sequence of the DNA the sensitivity of the analysis is increased several 100-fold, making the detection possible with stable, non-radioactive and inexpensive biotinylated oligonucleotides. We have applied this method (polymerase chain reaction (PCR] to the detection of the Z-mutation in the alpha-1-antitrypsin gene. After amplification, dot-blots of amplified DNA were subjected to hybridization with allele specific biotinylated oligonucleotide probes and washed at temperatures giving allele specificity. The bound biotin was visualized with avidin conjugated alkaline phosphatase using 5-bromo-4-chloro-3-indolylphosphate and nitro blue tetrazolium as colour reagents. The detection can be performed on less than 1 microgram genomic DNA, and is therefore applicable on small amounts of blood, fibroblasts and chorionic villus biopsies.

Base Sequence↗

[Transdermal scopolamine to prevent postoperative nausea and vomiting after uterine curettage and termination of pregnancy. A double-blind clinically controlled study with placebo].

A randomized double-blind clinically controlled investigation with a placebo was undertaken to investigate the prophylactic effect of transdermal scopolamine on postoperative nausea and vomiting after dilatation and curettage and termination of pregnancy. No significant difference was found between the placebo and transdermal scopolamine. On the other hand, the patients in the scopolamine group had significantly more postoperative discomforts which were attributable to the anticholinergic effect of scopolamine. Transdermal scopolamine cannot be recommended for the prophylaxis of postoperative nausea and vomiting following uterine curettage and termination of pregnancy.

Abortion, Induced↗

Metric results of vestibuloplasty in unilateral cleft patients.

Vestibuloplasty was performed on patients with completely closed cleft lip/alveolus or cleft lip/palate, using a mesh of polyglactin for covering the epithelial defect on the alveolar process. The vestibular height in the region of the teeth adjacent to the cleft was measured in 19 cases (average age 7.1 years) immediately before and after surgery as well as 4-10 months later. Although a loss of height of 18% had occurred during the healing period, the original height at the mesial tooth was increased from 6.0 mm to 11.2 mm and at the distal tooth from 3.7 mm to 11.4 mm. This high and freely mobile vestibule of the mouth is considered to be a precondition for undisturbed growth of the orofacial system in cleft patients.

Adolescent↗

Sheltering--a protective measure following an accidental atmospheric release from a nuclear power plant.

The effectiveness of sheltering the population for reducing radiological effects following an accidental release of radioactivity at a nuclear power plant was investigated. Different levels of respiratory protection and the administration of a thyroid blocking agent were also studied as possible complements to sheltering. Specific conditions were assumed, concerning the high protection factors of regular buildings and the high availability of civil defense shelters. Computations were performed by means of a probabilistic consequence model, which allows a comprehensive description of exposure modes and processes dealing with the implementation of sheltering and which takes into account a broad range of radiological effects. Sheltering, even in regular buildings, was found to be efficient in reducing early fatalities and other non-stochastic effects. However, it was shown that respiratory protection is also needed in order to alleviate stochastic effects and that, for this purpose, expedient individual filtration methods may be satisfactory. Under the conditions studied, sheltering was found to be preferable in most cases over evacuation, as the main immediate protective measure, unless evacuation can be carried out before the radioactive cloud reaches the populated area.

Accidents↗

[Behavior of respiratory tract, esophagus and pulmonary artery pressure in bronchoscopies in normofrequent jet ventilation in comparison with Friedel's ventilation technics].

The dynamics of selected physiological respiratory parameters were studied in a total of 29 patients. During slight hyperventilation and good oxygenation by both Friedel's and jet ventilation (driving pressure 0.3 and 0.4 MPa, respectively), comparably low respiratory tract pressures were observed. Transmission to intrathoracic (44-46%) and mean pulmonary artery pressure (11-13%) indicates only a low-grade ventilation-induced hemodynamic influence. By contrast, clear increases in pulmonary artery pressure due to intubation were recorded. Thus, the employed normofrequent jet ventilation with its continuous open-tube ventilation which is independent of the undisturbed bronchological examination possesses beneficial properties from a cardiorespiratory view.

Adult↗

Improved methods for the detection of unique sequences in Southern blots of mammalian DNA by non-radioactive biotinylated DNA hybridization probes.

Biotinylated DNA hybridization probes offers a stable, cheap and non-radioactive alternative to probes labelled with 32P. Insufficient sensitivity has, however, up till now, been prohibitive for the use of such probes in detecting unique sequences in Southern blots of human DNA. By optimizing the steps in the procedure we have improved the sensitivity enough for such use. We have showed (1) that long probes (greater than 500 nucleotides) perform unproportionally better than short probes; (2) that a simple affinity labelling with avidin alkaline phosphatase conjugate performs better than laborious immunochemical systems; (3) that use of 3% BSA as blocking agent at 37 degrees C and the presence of 0.5 mol/l NaCl together with 1% BSA during the affinity labelling nearly eliminate background staining; (4) that a dramatic gain in sensitivity is gained by affinity labelling at pH 9.0 instead of 7.5; (5) that biotin-labelling can be highly reproducibly performed on a preparative scale with cheap and easily synthesized bio-11-dUTP in a two step nick-translation and (6) that biotinylated probes and hybridization mixtures can be stored for months and reused. The study has resulted in the presentation of a fast procedure, which is generally applicable to routine DNA diagnostic work, also in parts of the world where it is difficult to get a regular supply of 32P.

Base Sequence↗

[Condoms--AIDS].

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

In vitro susceptibility of Mycobacterium avium complex to antibacterial agents.

In vitro agar dilution susceptibility studies were performed utilizing 20 isolates (24 against rifamycin) of Mycobacterium avium complex against several antimicrobial agents not routinely tested in the mycobacteriology laboratory. Thirteen strains were susceptible to gentamicin at 4 micrograms/ml, 20 to amikacin at 8 micrograms/ml, 18 to streptomycin at 8 micrograms/ml, 20 to kanamycin at 8 micrograms/ml, 20 to trimethoprim/sulfamethoxazole at 2 micrograms/ml, 12 to sulfisoxazole at 10 micrograms/ml, 14 to rifabutin at 1 microgram/ml. No activity was found with penicillin G, cephapirin, moxalactam, vancomycin, clindamycin, erythromycin, trimethoprim, or minocycline. This data suggests a potential use of trimethoprim/sulfamethoxazole, sulfisoxazole, amikacin, gentamicin, and kanamycin in the treatment of infections caused by this group of organisms.

Anti-Bacterial Agents↗