δ-aminolevulinic acid dehydrase (porphobilinogen synthase) in two families with inherited enzyme deficiency

The inheritance of a deficient delta-aminolevulinic acid dehydrase (ALA-D; synonym: porphobilinogen synthase; EC 4.2.1.24) was studied in blood samples of two families over three generations. The propositus in each family was a young male acute hepatic porphyria patient with an almost complete ALA-D deficiency in the homozygous state (ALA-D activity less than 2% of controls). Heterozygotes are clinically non-affected (mean ALA-D 36% of controls). The mode of transmission could be traced by enzyme activity and electrophoretic polymorphism studies. Heterozygotes are detected by the demonstration of enzyme activity in the gel. The notation D was used for the gene expressing the defective enzyme. The "phenotype" D-1 was observed in six, the "phenotype" D-2 in three of all heterozygotes studied. These results are compatible with a single normal allele in heterozygotes responsible for enzyme activity. Quantitative assays and the segregation pattern in both families suggest a 3-allele-system for the inheritance of ALA-D deficiency.     

Polymer diffusion in mixtures of polystyrene and polymethylstyrene studied by forced rayleigh scattering and photon correlation spectroscopy

Tracer diffusion coefficients D^* of both components were measured in mixtures of polystyrene (PS) and polymethylstyrene (PMS), a random copolymer from 60 wt.-% of m-methylstyrene and 40 wt.-% of p-methylstyrene. The results are interpreted in terms of the free-volume theory which yields master curves even for “asymmetric” mixtures of oligomer and polymer chains, if D^* is drawn versus the distance from the glass transition temperature, T–T_g. Whereas D^* was measured by the forced Rayleigh scattering technique, we also studied photon correlation spectroscopy in these mixtures and observed “slow modes” with decay constants that correspond to diffusion coefficients 2–3 decades smaller than the interdiffusion coefficient.     

Über die Grenzbedingungen von Zelleben und spezifischer Zellfunktion am isolierten Muskel

Zusammenfassung 1. Es werden an quergestreiften Muskeln (Zwerchfell, Herzvorhof von Warmblütern, Froschherz) unter den Bedingungen von Substratund Sauerstoffmangel Funktion und histologischer Zustand verglichen.2. Drosselung der Energiezufuhr führt in jedem Falle zu negativer Inotropie und diastolischem Stillstand. Dies führt zu dem zwingenden Schluß, daß die Kontraktion und nicht die Erschlaffung den energieverbrauchenden Teil des Kontraktionsvorganges darstellt.3. Gleichzeitiger Glucose- und Sauerstoffmangel führt erst mit dem Erlöschen der Glykogenolyse zur Kontraktur, die nach völligem Glykogenschwund irreversibel wird (Totenstarre).4. Die Totenstarre wird als Modellkontraktion abgelehnt.5. Aus den untersuchten Mangelbedingungen läßt sich eine Reihenfolge der Energieausnützung für den quergestreiften Muskel ableiten, wobei wesentliche Unterschiede zwischen Warmblüter und Kaltblüter bestehen.Mit 7 Textabbildungen     

Brown and Eccles'' Depiction of Vagal Effects: An Old and Widely Used Method Reexamined

It can be shown that the procedure for representing the effect of the vagal innervation of the heart introduced by Brown and Eccles in 1934 distorts the actual course of the inhibitory effect. A corrected procedure is proposed. It is stressed that cycle phase specificity of the stimulation can be studied only by drawing different curves representing the course of the vagal effect for different times of stimulation within the cardiac cycle.     

Perceptual Performance as a Function of Intra-Cycle Cardiac Activity

The purpose of the experiment was to test the hypothesis of a systematic change in perceptual performance within a single cardiac cycle due to the activity of the baroreceptors in carotid sinus. As an index of perceptual performance the d_s-parameter from signal detection theory (TSD) was used. A 1000 Hz sine tone had to be detected in a background of white noise. Each of 4 subjects received on the average 4605 noise or noise plus tone stimuli distributed over 10 experimental sessions. When comparing performance during time intervals before and after baroreceptor activity onset no significant difference was found. Also, when tracing perceptual performance over the whole cardiac cycle in steps of 66,100, and 200 msec, no systematic variation could be detected. For steps of 33 msec a rhythmic pulsation of perceptual performance of about 8 Hz appeared. An influence of electrical activity of the brain on perceptual performance was postulated. This activity would have to be time-locked to carotid sinus baroreceptor activity.     

Depressive symptoms and disability in acute and chronic back pain patients

Depression and level of disability are evaluated in acute and chronic low back pain (LBP) patients. To assess the possibility that some somatic symptoms are confounded with pain, the items of the Beck Depression Inventory arc divided into a cognitive-affective and somatic subscale. The sample consisted of 37 chronic LBP patients. 41 acute LBP patients, and 28 healthy participants. The level of disability was assessed by the Oswestry Low Back Pain Disability Questionnaire. Chronic LBP patients, but not acute LBP patients, have more depressive symptoms than controls. Additionally, chronic LBP patients report more somatic symptoms of depression (e.g.. emo ltional and self disturbance complaints) than cognitive-affective symptoms. Finally, correlation statistics reveal significant relations between the level of disability and depression scores. Whereas chronic patients show a significant correlation between the somatic subscale and level of disability, in acute patients the cognitive-affective subscale is significantly related to the level of disability. The findings suggest careful consideration of whether somatic symptoms of depression are related to pain when using self-report measurements of depression in pain patients. The separation of cognitive-affective and somatic symptoms of depression to evaluate pain problems seems appropriate.     

Studies with a pathogenic and an attenuated strain of Venezuelan equine encephalitis virus and aedes aegypti (L.) mosquitoes

Summary Venezuelan equine encephalitis virus was passaged in KB cell cultures. The virus lost its mouse pathogenicity following subcutaneous inoculation during KB cell passage; the attenuated strain also produced smaller plaques than the pathogenic strain. Both strains grew to the same extent inAedes aegypti (L.) mosquitoes after intrathoracic inoculation. If any reversions to pathogenicity occur during development of the attenuated virus in mosquitoes, then the mutation frequency per duplication per particle must be smaller than 3.5×10^–6.     

Production of IL-12, IL-23 and IL-27p28 by bone marrow-derived conventional dendritic cells rather than macrophages after LPS/TLR4-dependent induction by Salmonella Enteritidis

Induction of the interleukin-12 (IL-12) cytokine family comprising IL-12, IL-23, IL-27, and IL-12p40 by intracellular pathogens is required for orchestration of cell-mediated immune responses. Macrophages (MΦ) have been shown to be a source of IL-12 following TLR4-dependent activation by Salmonella (S.). In this study another antigen-presenting cell type, the conventional dendritic cell (cDC), was analyzed and its cytokine responses compared with those of MΦ. We generated bone marrow-derived conventional dendritic cells (BMDC) and macrophages (BMMΦ) by incubating murine bone marrow cells with supernatants containing granulocyte/macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), respectively. Stimulation of BMDC and BMMΦ with S. enterica serovar Enteritidis (SE) or LPS resulted in the release of IL-12 and IL-23 by BMDC but not by BMMΦ. Furthermore, BMDC secreted approx. 20-fold more IL-12p40 and IL-27p28 than BMMΦ. However, BMDC and BMMΦ produced similar levels of IL-10. Using BMDC originating from wild-type (wt), TLR2^def and TLR4^def mice, we show that in BMDC the induction of IL-12, IL-23, and IL-27p28 by SE is dependent on TLR4, whereas low-level production of p40 is also mediated by pattern recognition receptors (PRR) other than TLR4. Interestingly, LPS- and SE-provoked responses of BMDC were remarkably similar indicating that LPS is the primary danger molecule of SE. Taken together, our results point to cDC rather than MΦ as the major producers of the IL-12 family members during in vitro infection with SE. The mechanisms of recognition of SE, however, appear to be the same for cDC and MΦ     

Radiopharmacokinetics and radiation dose from 99mTc-HM-PAO (Preliminary report)

Whole body retention measurements were performed in volunteers after i.v. injection of ^99mTc-HM-PAO (Ceretec^®). The organ accumulation was measured in mice and data were transferred to standard man according to ICRP. Absorbed dose calculations were made with these data by using the concept of absorbed fractions (MIRD method). In man, the whole body retention and the retention in the brain could be calculated by direct measurement, absorbed doses to the other organs could only be derived from animal data. The absorbed dose to the brain derived from human data (10.3 Gy/MBq) is greater by a factor of 2 than that derived from animal data. The highest absorbed dose was received by the thyroid (24.4 Gy/MBq), the absorbed dose to the ovaries, testes and whole body ranged from 2.8 to 4.2 Gy/MBq.Dedicated to Professor Dr. Guenter Liess on the occasion of his 65th anniversary