Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli

Substitution therapies for orphan genetic diseases, including enzyme replacement methods, are frequently hampered by the limited availability of the required therapeutic substance. We describe the isolation of a pterin intermediate from bacteria that was successfully used for the therapy of a hitherto incurable and lethal disease. Molybdenum cofactor (Moco) deficiency is a pleiotropic genetic disorder characterized by the loss of the molybdenum-dependent enzymes sulphite oxidase, xanthine oxidoreductase and aldehyde oxidase due to mutations in Moco biosynthesis genes. An intermediate of this pathway-'precursor Z'-is more stable than the cofactor itself and has an identical structure in all phyla. Thus, it was overproduced in the bacterium Escherichia coli, purified and used to inject precursor Z-deficient knockout mice that display a phenotype which resembles that of the human deficiency state. Precursor Z-substituted mice reach adulthood and fertility. Biochemical analyses further suggest that the described treatment can lead to the alleviation of most symptoms associated with human Moco deficiency.     

Possible effect of gender and season on the length of hospitalisation in unipolar major depressives

BACKGROUND: Seasonal variation as well as gender differences of several phenomena of affective disorders are a common topic of interest. METHODS: The authors analysed the possible effect of season and gender on the length of hospital stay in 529 in-patients with unipolar major depressive episode. RESULTS: Age and menopausal status alone did not influence the length of hospitalisation but there was a statistical tendency (only for females) for the shortest hospital stay in summer, that reached significance in females younger than 50 years. CONCLUSIONS: The results suggest a possible seasonal and gender effect on recovery from major depression. LIMITATIONS: Retrospective nature of the study, lack of systematic assessment of clinical response and no data collection about marital status and living conditions, that also can influence the time of discharge.     

The effect of stimulus velocity on the response of movement sensitive neurons of the frog's retina

Summary 1. By means of metal-filled micropipettes the action potentials of 4 different classes of optic nerve fibers were recorded in Rana esculenta. The relationship between the angular velocity of the stimuli and the neuronal response was determined.2. If an object smaller than the excitatory receptive field (ERF) was moved through the receptive field of the different classes of retinal units the response depended on the angular velocity, contrast and size of the stimulus. The response was measured as the average impulses frequency (R) during the traverse of the ERF. Between R and the angular velocity (v) the equation R=k·v ^c [impulses · sec^–1] was found. The exponent c was 0.5 for class 1 neurons, 0.7 for class 2 neurons, and 0.95 for class 3 neurons. In class 4 neurons the response to large stimuli increased linearly with the increase of the angular velocity, while no systematic relationship between R and v was valid for small moving stimuli (<5°)3. If the contrast or the size of the stimuli was changed the exponent c was not changed; but k depended on both parameters and on the direction of the contrast against the background. The power function was no longer valid if stimuli considerably larger than the ERF were used. The exponent c was independent of the type of the movement (linear, non-linear, irregular movement); it was also independent of the direction of the motion.4. A model of the receptive field is demonstrated. In this model an RC-filter function within the bipolar cells is assumed. The bipolar cells with different filter function activate different classes of ganglion cells. Different time constants of the bandpass filter at the bipolar cell level are the main cause for the different exponents of the power function between angular velocity and neuronal response.     

Kollagenfolien als temporärer Hautersatz. Klinische und patho-anatomische Untersuchungen

Zusammenfassung Im Kaninchenversuch wurde eine neue Kollagenfolie (COL 65–70, 65–71) im Vergleich mit Polypyrrolidonpulver, Teflonfilz und unbehandelten Kontrollen zur temporären Hautdeckung nach flächenhafter Hautverbrennung getestet. Bei der verwandten Kollagenfolie handelt es sich um gereinigtes tierisches Kollagen, das nach seiner Lösung wieder gefällt wurde. Nach einem patentierten Verfahren wurden hierbei die Moleküle wieder ausgerichtet, so daß eine gewisse physikalische Festigkeit gewährleistet ist. Ein Weichmacherzusatz bewirkt die Geschmeidigkeit. Zur Verhinderung der unerwünschten Austrocknung nach Auflage auf die Wundfläche wurde die Kollagen-Gelplatte mit einer härteren Kollagenfolie abgedeckt. Eine feingeweblich erfaßbare Abwehrreaktion des Wirtsorganismus gegen die Kollagenfolie bzw. eine entzündliche Demarkation konnte an unserem Versuchskollektiv nicht nachgewiesen werden.

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Summary Along with polypyrrolidon powder and teflon felt, a new collagen foil has been evaluated for the temporary closure of skin defects caused by experimental third degree burns in rabbits. A control serics remained untreated. The collagen foil applied was obtained from animal connective tissues the fibrils of which were regenerated after liquefaction. According to a patent procedure the collagen molecules were reconverted. By the addition of a weakener the flexibility of the foil could be changed. In order to avoid an undesired exsiccation after covering the burn wound the collagen foil was protected by a tanned collagen film layer. In the present material, no defensive reactions of the recipient organisms against the collagen foil nor any inflammatory demarcations could be noticed by means of microscopic examination.

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Herrn Prof. Dr. Drs. h. c. Dr. h. c.K. H. Bauer zum 75. Geburtstag in Verehrung und Dankbarkeit zugeeignet.     

Antibiotic sensitivities of urinary pathogens, 1971-8.

The sensitivites of urinary pathogens from general practice and from hospital to a range of antimicrobial drugs have been recorded for the period 1971-8. There have been changes in the proportions of the different bacterial species and in their sensitivites to antibiotics. In particular, the position of ampicillin/amoxycillin and cephalosporins has deteriorated, partly because more resistant species have somewhat increased in prevalence and partly because the usually sensitive species, such as Escherichia coli, have become more resistant. Over the period 1971-8 the sensitivity of urinary pathogens, whether in general practice or in hospital, to co-trimoxazole and to trimethoprim has been maintained at a high level.     

Voluntary HIV counseling and testing: experience among the sexually active population in Bangui,Central African Republic

OBJECTIVES: In July 1997, the National Reference Center for Sexually Transmitted Diseases of Bangui, Central African Republic (CAR), was expanded by the creation of an anonymous and voluntary counseling and testing (VCT) unit for HIV infection, the Anonymous Surveillance Unit (Unité de Dépistage Anonyme [UDA]). The goal of the UDA was to initiate and promote voluntary HIV testing in the general adult population of Bangui. We carried out an observational and comprehensive survey over a 4-year period to document and analyze the experience of VCT in the UDA, with special attention to risk factors associated with HIV infection. METHODS: All clients for VCT were given adequate pretest counseling by trained counselors focused on knowledge about HIV infection and sexually transmitted infections, individual risks of acquiring HIV, and anticipation of the client's attitude about test results. After consent was obtained, a blood sample was drawn and tested for HIV by two ELISAs in parallel. The client paid a standard cost of $1.20 at the initial visit. After a week, test results were given to the client during the posttest visit, at which time HIV-seropositive individuals received emotional support and were referred to specific social or medical structures. Seronegative clients received reinforcement of prevention messages and were asked to come back for serologic follow-up free of charge after 3 (M3) and 12 (M12) months. RESULTS: From July 1997 to March 2001, 5686 individuals aged 14 to 65 years (mean age, 27 years) had an initial visit for VCT (V1). Peaks of UDA visitation (250-450 clients) were observed on the annual AIDS Day in the CAR, at which time HIV serologic testing was offered free of charge. A total of 5060 (89%) clients came back for a second visit (V2) to receive test results. Among those, 18.3% were infected with HIV type 1. Multivariate analysis of risk factors demonstrated marked association of HIV seropositivity with age, female gender, widowed/divorced women, poor or low education level, occupations such as civil servants or merchants, presence of symptoms of sexually transmitted infections, and lack of systematic condom use. Single young women were at higher risk for HIV infection compared with men of the same age (OR = 7.7 for women aged 15-24 years, 95% CI: 4.0-14.0; OR = 2.8 for women aged 25-34 years, 95% CI: 1.7-4.5). Widowed women older than 44 years of age were more likely to be HIV-seropositive than men (OR = 10.0; 95% CI: 1.7-83.6). A total of 885 (21%) HIV-seronegative individuals returned for follow-up at 3 months (M3; 0.45% rate of seroconversion). Seventy-nine (9%) individuals returned at 12 months (M12), without any new cases of HIV infection. HIV-negative clients consulting at M3 and M12 showed a significant reduction in unprotected intercourse with occasional sexual partners. CONCLUSION: This experience demonstrates that VCT for HIV infection is feasible in Central Africa.     

Sigma-movement and optokinetic nystagmus elicited by stroboscopically illuminated stereopatterns

Summary Sigma-movement is an apparent movement seen when a stationary periodic visual pattern of the period P_s is illuminated Stroboscopically at the flash frequency f_s and smooth gaze pursuit eye movements are performed across the pattern at an angular velocity V_e = P_s · f_s deg · s^–1. Sigma-movement leads to an optokinetic nystagmus (Sigma OKN) which in turn sustains Sigma-movement perception. (1) Sigma-movement was also seen in an apparent three-dimensional periodic stripe pattern generated by two periodic monocular stimulus patterns with a certain degree of horizontal binocular disparity. (2) Sigma-movement perception and Sigma-OKN were also elicited by a Stroboscopically illuminated, stationary, random dot stereostripe pattern. The periodicity P_s of this pattern is generated on the cyclopean retina (Julesz 1971). The equation described above was also valid. When the time delay t between left eye and right eye flashes was varied, the apparent depth of the random dot stereostripe pattern decreased with increasing t, but the Sigmaeffects were not affected. (3) Sigma-movement illusion and Sigma-pursuit movements can also be induced when real three-dimensional objects composed of periodic components are Stroboscopically illuminated and adequate gaze or eye pursuit movements are induced. Sigma-movement is related to gaze movement and is therefore elicitable by eye, head or body movements. (4) Sigma-movement is presumably caused by the interaction of efference copy signals (generated in a cortical gaze pursuit system) and afferent visual signals. The present data indicate that neuronal mechanisms for this interaction are located — at least in part — at or beyond the level of binocular fusion and stereopsis.Supported by grants of the Deutsche Forschungsgemeinschaft (Gr161)     

HBcAg-specific cytokine production by CD4 T lymphocytes of children with acute and chronic hepatitis B

In the presented studies HBcAg-specific cytokine production (IFN-gamma, IL-2, IL-4, IL-5 and IL-10) was evaluated, by Th lymphocytes isolated from peripheral blood of children with acute or chronic B hepatitis. Moreover, effect of IL-10 neutralization was examined on HBcAg-induced secretory response of Th lymphocytes obtained from children with chronic B hepatitis. The studies were performed on 12 children with acute self-limited B hepatitis and 20 children with chronic active B hepatitis. CD4 T cells were isolated from peripheral blood of the patients, cultured for 48h in presence of rHBcAg or in its absence (control). Production of studied cytokines was monitored using ELISPOT and ELISE assays. The course of acute self-limited B hepatitis was associated with preferential Th1-type response, manifested by elevated production of IFN-gamma and IL-2. On the other hand, in chronic B hepatitis a diminished response to HBcAg of both Th1 and Th2 types was disclosed, characterized by very low secretion of IFN-gamma, IL-2, IL-4 and IL-5. In parallel, preferential antigen-specific production of IL-10 was noted and its suppressive effect on HBcAg-induced response of Th1 cells. The results permitted to conclude that in children with acute self-limited B hepatitis preferential HBcAg-specific activation of Th1 lymphocytes may be of significance for efficient anti-HBV immune response. On the other hand, development of chronic B infection in children seems to be determined by disturbed HBcAg-specific functions of both Th1 and Th2 cells whereas activity of the disease may be controlled by anti-inflammatory response of antigen-presenting cells and/or of regulatory CD4 T lymphocytes, involving IL-10 production.