Characterization of ferrochelatase (hemH) mutations in Haemophilus influenzae

Haemophilus influenzae lacks most of the biosynthetic enzymes for hemin synthesis. However, the organism has retained ferrochelatase activity, which we identified to be encoded by a hemH-homologous gene. In this report we characterize the growth physiology conferred by hemH mutations under infection and laboratory conditions.     

Changed visuomotor transformations during and after prolonged microgravity

A series of step-tracking experiments was conducted before, during, and after a 3-week space mission to assess the effects of prolonged microgravity on a non-postural motor-control task. In- and post-flight accuracy was affected only marginally. However, kinematic analyses revealed a considerable change in the underlying movement dynamics: too-small force and, thus, too-low velocity in the first part of the movements was mainly compensated by lengthening the deceleration phase of the primary movement, so that accuracy was regained at its end. The observed in-flight decrements in peak velocity and peak acceleration point to an underestimation of mass, in agreement with the re-interpretation hypothesis of Bock et. al. Post-flight no reversals of the in-flight changes (negative aftereffects) were found. Instead, there was a general slowing down, which could be due to post-flight physical exhaustion.     

Event-Related Potential Correlates of Two Stages of Information Processing in Physical and Semantic Discrimination Tasks

Event-related potentials were studied while subjects performed physical and semantic discrimination tasks. Two negative components, N_A and N2, were observed in both kinds of discriminations. The earlier component, N_A, had a constant onset latency, but its peak latency varied as a function of stimulus complexity. N2 latency varied in relation to changes in the peak of N_A. RT and P3 followed N2 by similar amounts of time across tasks. The N_A and N2 components were interpreted as reflecting partially overlapping sequential stages of processing associated with pattern recognition and stimulus classification, respectively.     

The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts

Establishing and maintaining mature bone at the bone–device interface is critical to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and dental implants results in implant failure. Considerable effort has been devoted to alter the surface characteristics of these biomaterials in order to improve the initial interlocking of the device and skeleton. We investigated the effect of surface chemistry modification of titanium alloy (Ti–6Al–4V) with zinc, magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation of key intracellular signalling proteins in human bone-derived cells (HBDC) cultured on these modified Ti–6Al–4V surfaces. Western blotting demonstrated that modifying Ti–6Al–4V with CHAP or Mg results in modulation of key intracellular signalling proteins. We showed an enhanced activation of Shc, a common point of integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway was also upregulated, suggesting its role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the Mg and CHAP modified Ti–6Al–4V. Thus surface modification with CHAP or Mg may contribute to successful osteoblast function and differentiation at the skeletal tissue–device interface.     

A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor

The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development.     

Die Erythrokinetik bei Osteomyelofibrose

Zusammenfassung Bei 20 Patienten mit Osteomyelofibrose wurden Erythrocytenbildung und Erythrocytenzerstörung mit Hilfe von Cr⁵¹ und Fe⁵⁹ z. T. nach simultaner Verabreichung dieser Isotope untersucht. Die Erythrocytenlebensdauer war oft verkürzt, jedoch meist nicht hochgradig. Nur bei wenigen Kranken war eine aktive Beteiligung der Milz an der vorzeitigen Zerstörung der Erythrocyten nachweisbar. Das Plasmaeisenturnover war fast stets erhöht, die Eiseninkorporation in die Erythrocyten vermindert. Eine extramedulläre Erythropoese war meist, aber nicht ausnahmslos, durch Oberflächenmessung nachzuweisen. Sie fand überwiegend in der Milz statt, doch war die Leber in zwei Fällen der wichtigste Ort der Erythrocytenbildung. Eine Produktion von Erythrocyten im Knochenmark war bei der Hälfte der entsprechend untersuchten Fälle noch in geringem Maße vorhanden. Die komplexe Korrelation dieser Befunde mit den hämatologischen Daten wurde besprochen und die Indikation zur Splenektomie erörtert.

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Summary Production and destruction of erythrocytes were investigated in 20 patients suffering from myelofibrosis. Cr⁵¹ and Fe⁵⁹ were administered simultaneously. The erythrocyte life span was shortened frequently, but only moderately in most instances. In few patients only the spleen played an active part in the accelerated red cell destruction. The plasma iron turnover was increased in most cases, the incorporation of iron into the erythrocytes was decreased. Extramedullary erythropoiesis was demonstrated by means of surface activity measurements in most but not in all patients. It was localised most frequently in the spleen. In two cases, however, the liver was the most important site of erythrocyte production. Some degree of medullary erythropoiesis was seen in 50 percent of our cases. The correlation between these results and the remaining hematological findings as well as the question of when to remove the spleen are discussed.

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Unter technischer Mitarbeit von FräuleinRenate Roesch, FräuleinMargret Philips und FräuleinIngrid Westmattelmann.

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Die Arbeit wurde durchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.     

HEp-2 Cell-Adherent Escherichia coli and Intestinal Secretory Immune Response to Human Immunodeficiency Virus (HIV) in Outpatients with HIV-Associated Diarrhea

HEp-2 cell-adherent Escherichia coli and the human immunodeficiency virus (HIV) itself have recently been incriminated as causes of chronic HIV-associated diarrhea. This study sought to determine the prevalence of these two agents among HIV-infected patients with diarrhea in an outpatient setting in the United States and to compare their prevalence to that of other commonly recognized enteropathogens known to be present in this population. HEp-2 cell-adherent E. coli was found in 20 of 83 (24.1%) patients with diarrhea. A diffuse pattern of adherence was the most common, found in 14 of 20 (70%) patients, followed by a localized adherence pattern (6 of 20; 30%). An intestinal secretory immune response against the p24 antigen of HIV was found in 9 of 34 (27.5%) patients with HIV-associated diarrhea. The following pathogens or products were also detected in lower frequencies: Cryptosporidium spp. (10.8%), Clostridium difficile toxin (8.8%), microsporidia (6%), Isospora belli (3.6%), Blastocystis hominis (2.4%), Giardia spp. (1.2%), Salmonella spp. (1.2%), and Mycobacterium spp. (1.2%). The role of HEp-2 cell-adherent E. coli and HIV enteric infections in patients with HIV-associated diarrhea deserves further study.     

Phosphate transport in brush border membrane vesicles isolated from renal cortex of young growing and adult rats

Recent clearance studies have demonstrated that the maximal tubular reabsorption of inorganic phosphate (Pi) per ml of glomerular filtrate (max. TRPi/ml GF) of the whole kidney is markedly lower in adult than in young growing rats fed either normal (0.8 g%) or low (0.2 g%) phosphorus diet. In addition, in adult rats clearance studies indicate that enhancement of max. TRPi/ml GF is observed 21 days but not 8 days after starting the low (0.2%) phosphorus diet. In the present work we have studied in the same experimental condition the Na⁺-dependent Pi uptake in brush border membrane vesicles (BBMV) isolated from renal cortex of either young growing or adult rats. The results of this study indicate that under the low (0.2%) but not under the normal (0.8%) phosphorus diet the Na⁺-dependent Pi uptake by BBMV was significantly depressed in adult as compared to young growing rats. In adult rats the Pi transport response to Pi restriction monitored at the brush border membrane level was different from that observed by clearance studies in the whole kidney. Indeed, the Pi uptake by BBMV was already enhanced after 8 days of Pi restriction and it did not increase further when studied 21 days after starting the low (0.2%) phosphorus diet. These results suggest that the regulation of the overall transfer of Pi across the renal epithelium may involve other additional modulating factors than the Na⁺-dependent Pi transport system present in the luminal membrane of the proximal tubule.     

Detecting depressive disorders in drug abusers : A comparison of screening instruments

Previous investigators have reported a high prevalence of depressive symptoms in drug-dependent patients. Given the responsiveness of depressive disorders to both psychological and pharmacological treatments, it is desirable to find an economical, efficient screening instrument to detect depressive disorders in this population. In this study, 6 depression symptom screening scales (Beck Depression Inventory, Hamilton Depression Scale, Raskin Depression Scale, Degree of Illness Rating, Symptom Checklist 90 Overall, and Depression Subscale) based on either clinician interview or patient self report, were compared according to their utility in detecting cases of depression among 64 applicants for treatment at a substance abuse treatment unit of a community mental health center. The criteria for a case of depression were the Research Diagnostic Criteria (RDC) which are specified and operationalized. Cases identified using previously described cutoff scores on the screening scales were compared to rates based on the RDC and sensitivity and specificity were determined. The results showed that: (1) although the sensitivity of the symptom scales was applicable, ranging from 65--94%, the specificity was less impressive, ranging from 39--61%, and (2) the Beck Depression Inventory, a 13-item patient self report was the most sensitive and specific and is recommended for screening drug-dependent populations for depression.     

Sensitivity to hymenoptera in adult males

The authors studied the sera of 86 selected adult male office workers for IgE antibodies to yellow jacket and honey bee venoms and to environmental inhalants and foods. Structured histories provide information about the experiences of these men with the Hymenoptera and other immunological information. Three men (3%) gave a history of a local or general reaction to the Hymenoptera but no antibodies were detected. Ten men (12%) had IgE antibodies to yellow jacket or honey bee venoms but none gave a history of a reaction. Nine of these men were atopic. The authors speculate that IgE antibodies to the Hymenoptera in atopic adult males may be more common than is currently recognized.