Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all menigiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.This study was supported by a grant of the Tumorzentrum Heidelberg/Mannheim (M.K., No. 10028060)     

Pars plana vitrectomy and direct diathermy for complications of multiple retinal angiomas.

A 16-year-old female had multiple retinal capillary angiomas, complicated by marked retinal and optic disc neovascularization, preretinal membranes, and retinal detachment in her right eye. Pars plana lensectomy, vitrectomy, fluid/gas exchange, direct transvitreal diathermy of the angiomas, endolaser scatter photocoagulation, and scleral buckling resulted in retinal reattachment and regression of the neovascularization. Although additional surgery was necessary for recurrent tractional retinal detachment, long-term retinal reattachment and stable vision was achieved following obliteration of all angiomas.     

Development ofDipetalonema viteae third-stage larvae (Nematoda: Filarioidea) in micropore chambers implanted into jirds,hamsters, normal and immunized mice

Summary Development of third-stage larvae ofDipetalonema viteae within subcutaneously implanted micropore chambers proceeded in all hosts tested up to the fourth-stage larvae and occasionally to adolescent worms. In the jird the timing of development was comparable to a natural infection. Although the mouse is an insusceptible host, larval development could take place, but was very slow. Two intraperitoneal inoculations of living thirdstage larvae into mice induced the production of antibodies against the larval cuticle and against common antigens. In such immune mice the development of third- and fourth-stage larvae within micropore chambers was significantly inhibited, larval mortality was increased, and the larval motility was impaired.     

Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells

Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into ‘neighborhoods’ comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.     

Effects of prolonged exercise at a similar percentage of maximal oxygen consumption in trained and untrained subjects

Summary Six trained male cyclists and six untrained but physically active men participated in this study to test the hypothesis that the use of percentage maximal oxygen consumption (% , as a normalising independent variable is valid despite significant differences in the absolute of trained and untrained subjects. The subjects underwent an exercise test to exhaustion on a cycle ergometer to determine and lactate threshold. The subjects were grouped as trained (T) if their exceeded 60 ml ·kg^–1 ·min^–1, and untrained (UT) if their was less than 50 ml · kg^–1 · min-^–1. The subjects were required to exercise on the ergometer for up to 40 min at power outputs that corresponded to approximately 50% and 70% The allocation of each exercise session (50% or 70% was random and each session was separated by at least 5 days. During these tests venous blood was taken 10 min before exercise (–10 min), just prior to the commencement of exercise (–10 min), after 20 min of exercise (20 min), at the end of exercise and 10 min postexercise (+ 10 min) and analysed for concentrations of cortisol, [Na⁺], [K⁺], [CI^–], glucose, free fatty acid, lactate [la-], [NH₃], haemoglobin [Hb] and for packed cell volume. The oxygen consumption ( ) and related variables were measured at two time intervals (14–15 and 34–35 min) during the prolonged exercise tests. Rectal temperature was measured throughout both exercise sessions. There was a significant interaction effect between the level of training and exercise time at 50% for heart rate ( _c:) and venous [la^–]. At 70% and ventilation ( ) for the T group and and carbon dioxide production for the UT group increased significantly with time and there was a significant interaction effect forf _c, ]Ia^–1], [Hb] and [NH₃]. The change in body mass at 50% and 70% was significantly greater in the T group. The present study found that when two groups of male subjects with different absolute exercised at a similar percentage of some effector responses were significantly different, questioning the validity of selecting % as a normalising independent variable.     

Norepinephrine and epinephrine responses during orthostatic intolerance in healthy elderly men

In young individuals, orthostatic intolerance is associated with marked increases in plasma epinephrine (EPI) concentrations and attenuated rises in plasma norepinephrine (NE) concentrations. This study investigated the cardiovascular, EPI and NE responses of healthy elderly males during orthostatic stress. Twelve men (68 +/- 1 yr) with a recent history of orthostatic hypotension and who exhibited orthostatic intolerance (HYPO) during 90 degrees head-up tilt (HUT) were compared with 12 men (69 +/- 1 yr) without a history of orthostatic hypotension and who remained normotensive (NORMO) throughout 90 degrees HUT. Beat-by-beat recordings of heart rate (HR), mean (MAP), systolic (SBP), diastolic (DBP), and pulse (PP) pressures were made throughout 90 degrees HUT. Blood samples obtained during supine rest and 90 degrees HUT were analyzed for changes in EPI and NE concentrations, hematocrit, hemoglobin and plasma volume. Compared to supine rest, orthostatic intolerance was characterized by significant reductions (p < 0.0001) in MAP, SBP, DBP, and PP. The HR, MAP, SBP, DBP, and PP at the termination of 90 degrees HUT was significantly lower (p < 0.0001) for HYPO than NORMO. The 90 degrees HUT position resulted in significant increases (p < 0.01) in NE for both HYPO and NORMO, with the rise in NE significantly lower (p < 0.05) in HYPO. There were no differences between groups regarding EPI concentrations at the termination of 90 degrees HUT. These results suggest that the magnitude of arterial pressure (AP) reduction does not influence the EPI response during orthostasis in healthy elderly men. However, marked reductions in AP, leading to orthostatic intolerance, are associated with inadequate increases in NE in these individuals.     

Physiological responses to intermittent and continuous exercise at the same relative intensity in older men

We investigated the physiological responses in older men to continuous (CEx) and intermittent (IEx) exercise. Nine men [70.4 (1.2) years, O_2peak: 2.21 (0.20) l min^–1; mean (SE)] completed eight exercise tests (two CEx and six IEx) on an electronically braked cycle ergometer in random order. CEx and IEx were performed at 50% and 70% O_2peak. IEx was performed using 60sE:60sR, 30sE:30sR and 15sE:15sR exercise to rest ratios. The duration of exercise was adjusted so that the total amount of work completed was the same for each exercise test. Oxygen uptake (O₂), minute ventilation (_E) and heart rate (HR) were measured at the mid-point of each exercise test. Arterialised blood samples were obtained at rest and during exercise and analysed for pH and PCO₂. At the same relative intensity (50% or 70% O_2peak), IEx resulted in a significantly lower (P<0.01) O₂, _E and HR than CEx. There were no significant differences (P>0.05) in O₂, _E and HR measured at the mid point of the three exercise to rest ratios at 50% and 70% O_2peak. pH and PCO₂ during CEx and IEx at 50% O_2peak were not significantly different from rest. CEx performed at 70% O_2peak resulted in significant decreases (P<0.05) in pH and PCO₂. There was a significant decrease (P<0.05) in pH only during the 60sE:60sR IEx at 70% O_2peak. Changes in arterialised PCO₂ during the 60sE:60sR, 30sE:30sR and 15sE:15sR at both 50% and 70% O_2peak exercise tests were not significant. When exercising at the same percentage of O_2peak and with the total amount of work fixed, IEx results in significantly lower physiological responses than CEx in older men. All results are given as mean (SE).