Two kinds of resting discharge in cat muscle spindles.

1. The behavior of primary endings of cat soleus muscle spindles was studied during shortening steps carried out at different muscle lengths. 2. Spindles were of two kinds: one, silent spindles, whose afferents fell silent after the shortening, at least over part of the range of lengths tested. The second, spontaneous spindles, resumed firing at all lengths. 3. For silent spindles, the duration of the silent period, measured at lengths where they did recover a resting rate, depended directly on muscle length and became shorter at longer lengths. This is what would be expected if the slack introduced in the spindle by the shortening step was removed more rapidly at longer lengths by the higher passive tension. For spontaneous spindles, on the other hand, the duration of the silent period after the shortening was largely independent of muscle length and depended on the spindle's rate of firing immediately before the shortening. 4. At intermediate lengths the discharge of slack spontaneous spindles remained unaffected by an isometric muscle contraction. It was therefore not possible to produce a pause in the discharge, behavior normally taken as typical of spindles. The discharge could be interrupted by the contraction if this was combined with a large shortening movement. 5. It is proposed that when intrafusal fibers are slackened by a shortening step, the resting discharge in spontaneous spindles is generated by a maintained depolarization of the annulospiral ending resulting from extension of the terminal coils by forces from within the receptor. A shortening contraction compresses the spirals to interrupt the discharge. The sensory endings of silent spindles remain below threshold until the spirals have been opened out sufficiently by external stretch.     

Recombinant 25-kDa CD23 and interleukin 1 alpha promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis.

Germinal centers contain a proliferating pool of centroblasts which give rise to non-dividing centrocyte. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescue. Rescue, in vivo, is likely to be dependent, initially, on interaction with antigen held on follicular dendritic cells (FDC). A subset of FDC located in that part of the germinal center furthest from centroblasts is particularly rich in CD23. Supernatants containing high levels of soluble CD23 were found not only to encourage the survival of germinal center B cells but also to promote their differentiation toward a plasmacytoid morphology; these activities were diminished following removal of CD23 from the supernatants. Recombinant 25-kDa CD23 was initially found to be incapable of providing the signal for germinal center cell development but on the addition of interleukin 1 alpha which, by itself, was inactive, rescue and differentiation of germinal center B cells were now achieved. Apoptosis in germinal center cells could also be prevented by the ligation of surface CD40 with monoclonal antibody: however, rescue via this pathway was not accompanied by plasmacytoid differentiation. These findings provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifurcation in the development of germinal center B cells following their rescue from apoptosis.     

Calcium dependence of histamine-induced increases in capillary permeability in isolated perfused rat hindquarters

Experiments were performed on isolated maximally vasodilated perfused rat hindquarters to evaluate the role of calcium and magnesium for the capillary permeability increase(s) elicited by histamine. Changes in capillary permeability were quantified by determinations of capillary filtration coefficient (CFC) with gravimetric technique, and capillary diffusion capacity (PS) for vitamin B12 (MW = 1,355) with a single injection indicator dilution technique. During control, vascular resistance was 2.2 PRU100 at a flow of 9.4 ml min-1 per 100 g, and PS for B12 was 3.7 +/- 0.1 ml min-1 per 100 g, while CFC was 0.0377 +/- 0.0004 ml min-1 mmHg-1 per 100 g. Perfusion with 'Mg-free' solution for 1 h caused a 24% increase in CFC, while neither 'Ca-free' perfusion nor perfusion with verapamil (5 X 10(-5) M) nor felodipine (1 X 10(-6) M) induced any changes in CFC. Histamine (100-200 microM) caused in all preparations a 150-200% increase in CFC with only small changes in PS for B12. This histamine effect was absent after 1 h of 'Ca-free' perfusion and was partially blocked after 1 h of perfusion with 0.1 mM calcium, while the calcium antagonists verapamil and felodipine had no effects on the histamine-induced changes. The results imply that histamine exerts its action on the endothelial cells through a calcium-dependent process, probably involving low affinity calcium sites but this process could not be inhibited by the calcium antagonists used. Thus, endothelial cell contractility, which probably is responsible for the histamine-induced increase in capillary permeability, exhibits unique characteristics, differing from those of vascular smooth muscle.     

Disposition of oxazepam in patients on maintenance hemodialysis

Summary The pharmacokinetics of a single 30-mg oral dose of oxazepam was evaluated in seven patients with chronic renal failure on maintenance hemodialysis and in seven healthy controls matched for age and sex. Based on total (free plus bound) serum oxazepam concentrations, elimination half-life was prolonged in renal patients compared to controls (22 vs 8 h,p<0.001) and volume of distribution increased (3.0 vs 1.4 1/kg,p<0.02). However, total clearance was similar between groups (1.8 vs 1.9 ml/min per kilogram). These findings were confounded by the increased oxazepam free fraction in serum of renal failure patients (10.3%) as compared to healthy controls (4.3%). Correction for differences in binding indicates similar distribution of unbound oxazepam between groups, but reduced clearance of pharmacologically active unbound oxazepam in renal patients (18 vs 45 ml/min per kilogram). Oxazepam dosage, therefore, may require downward adjustment for renal failure patients on hemodialysis.Supported in part by grant OC 10/6-3 from the Deutsche Forschungsgemeinschaft, and by grant MH-34223 from the United States Public Health Service     

Wertigkeit moderner Verfahren zur Lokalisation von Phäochromocytomen

Zusammenfassung Bei sechs Patienten mit adrenalem Phäochromocytom erfolgte die Lokalisationsdiagnostik durch Ultraschalluntersuchung, Phlebographie der Nebennieren und selektiver Katecholaminbestimmung im Blut der Vena cava sowie der Nebennierenvenen. Durch die selektive Katecholaminbestimmung konnten alle Phäochromocytome lokalisiert werden, durch die Ultraschalluntersuchung fünf, durch die Phlebographie vier. Ein Phäochromocytom von 1,5 g Gewicht, das nur durch die selektive Katecholaminbe-stimmung, nicht aber durch Ultraschall oder Phlebographie lokalisiert wurde, konnte computertomographisch dargestellt werden.Um Fehldiagnosen bei der selektiven Katecholaminbestimmung zu vermeiden, darf vor der Blutentnahme aus den Nebennierenvenen kein Röntgenkontrastmittel injiziert werden, da dies zu einer erheblichen Adrenalin- oder Noradrenalinfreisetzung aus dem Nebennierenmark führen kann.     

Comparative analysis of interferon and antiviral protein messenger RNAs.

A comparative analysis of interferon and antiviral protein messenger RNAs was carried out. Differences in their biological activities and sedimentation coefficients were found. In RNA preparations from superinduced cells (cells treated with poly(I).poly(C) and antimetabolites) and from cells treated with interferon, messenger RNAs possesing interferon and antiviral activities were detected. The results suggest the existence of two types of mRNA (for interferon and antiviral protein, respectively) and support the hypothetic model of interferon action via an antiviral protein.     

Magnetic carbohydrate nanoparticles for affinity cell separation

Magnetically responsive nanoparticles were prepared from enzymatically hydrolysed starch and magnetite. Two different monoclonal antibodies were covalently coupled to the particles. The antibody-coupled particles were in the size range of 100-300 nm and had an iron content of about 60%. Using 100 micrograms of magnetic particles (coupled with monoclonal mouse anti-rat Ig kappa light chain antibody) a very high depletion of surface Ig positive cells (mostly B-cells) from one million rat peripheral blood mononuclear cells could be achieved. The separation efficiency was evaluated by flow cytofluorometric analysis. This technique permits the detection of a small number of surface Ig positive cells among 10,000 negative cells.     

Glomeruläre Veränderungen nach Immunisierung mit heterologem Insulin

Zusammenfassung An 35 Meerschweinchen wurden nach Immunisierung mit reinem Rinderinsulin über 24–150 Tage die glomerulären Nierenveränderungen im Blindversuch an Semidünnschnitten quantitativ untersucht (Mesangiumvolumen, glomeruläre Zellzahl, Index of diabetic glomerular lesions) und, neben der Proteinurie, im Serum die Höhe des Antikörpertiters gegen Insulin (Insulinbindungskapazität) und der Cholesterin-, Harnstoff-und Albuminspiegel bestimmt. Mit zunehmender Dauer der Immunisierung kommt es zu einer Vermehrung der Mesangiumzellen um 57% gegenüber der Norm, zu einer Abnahme der Deckzellen, zu einer Verbreiterung des Mesangiums auf 12,4%, so daß stellenweise noduläre Mesangiumverbreiterungen beobachtet werden. Der IDGL nimmt gegenüber der Norm ab. Antikörper gegen das heterologe Insulin sind in jeder Phase der Immunisierung nachweisbar, während bei den übrigen Serumwerten (Harnstoff, Albumin) nach anfänglichen Veränderungen aller Werte eine spätere Normalisierung eintritt. Der Serumcholesterinspiegel ist auch in den Spätstadien der Immunisierung erhöht. Es kommt somit nach Immunisierung mit heterologem Insulin zu einer Proliferation ortsständiger glomerulärer Zellen im Sinne einer proliferativen intercapillären Glomerulonephritis, die morphologisch an die noduläre diabetische Glomerulosklerose erinnert und deren Ursache in einer Schädigung und funktionellen Störung des Mesangiums zu sehen ist.

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Glomerular changes induced by immunization with heterologous insulin

Summary In a blind-experiment with semi-thin sections we explored quantitatively the glomerular changes (mesangial volume, number of glomerular-cells, index of diabetic glomerular lesions) in 35 guinea pigs after immunizing them with pure beef insulin for 24–150 days. We determined the proteinuria, the serum-levels of the antibody-titer against insulin (insulin-binding capacity) and the levels of cholesterol, urea and albumin. After prolonged immunization the mesangial cells increased 57%. We found a decrease of the epithelial cells, and an increase of the mesangial volume to 12.4%, sporadically of a nodular character. The index of diabetic glomerular lesions decreased. Antibodies against heterologous insulin were demonstrable in every phase of immunization. After initial changes the other serum levels (urea, albumin) returned to normal. The level of serum-cholesterol increased late in immunization.The immunization with heterologous insulin resulted in a proliferation of glomerular cells like in a proliferative intercapillary glomerulonephritis. These changes resembled morphologically the lesions of nodular diabetic glomerulosclerosis and was caused by a functional disorder and injury of the mesangium.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft. Mit technischer Assistenz von Frl. S. Helber und Frl. R. Schnösenberg.

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Nach einem Vortrag auf dem IVth International Congress of Nephrology, Stockholm, Schweden, 23. 6. 69.     

Sex- and age-related blood pressure response to dynamic work with small muscle masses

Summary Four groups of subjects of different ages and sex (group I: 20–29 years, women; group II: 20–29 years, men; group III: 30–39 years, women; group IV: 30–39 years, men) undertook dynamic one-hand work (load range 40%–80% of maximum voluntary contraction, at 60 working cycles/min) to allow a study of cardiovascular responses as shown by the resultant changes in blood pressure and heart rate. During fatiguing dynamic one-hand work, there was a large increase in systolic and diastolic blood pressures in both sexes after a few minutes. For all load levels, the systolic blood pressure was found to be higher by about 4 kPa in men (groups II and IV) than in women (groups I and III). Other age-related differences became evident in the diastolic blood pressure changes. The values obtained for the older groups were higher than those in the two younger groups. These differences in blood pressure response are possibly due to sex-related differences in the release of catecholamines, or to age-related organic changes in the vessels.