Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function

Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25-44 years, mean 34; duration of diabetes 10-20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58 +/- 0.79 microV v. 7.34 +/- 1.12 microV; p less than 0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p less than 0.05) during ARI in AN patients.     

Application of antigens fromTaenia hydatigena cyst fluid for the immunodiagnosis of human hydatidosis

Fluid was collected from cysts ofTaenia hydatigena in 60 adult sheep and fluid from each animal pooled separately. By double diffusion antigen 5 was demonstrated in all pools but one. The criteria are described for selection and standardization of these preparations for use as antigens for the immunodiagnosis of human hydatid disease. Sera from 50 persons harbouring hydatid cysts and from 50 patients with other disease conditions were examined by the arc-5 double-diffusion test, using two antigens prepared fromEchinococcus granulosus andT. hydatigena cyst fluids, respectively. The results showed that a higher diagnostic sensitivity was obtained with the hydatid antigen. The significance of the findings is discussed in terms of their application to human immunodiagnosis in areas where hydatidosis, but not cysticercosis, is rare in livestock.     

Experimental Escherichia coli ascending pyelonephritis in rats: changes in bacterial properties and the immune response to surface antigens.

Systemic and urinary antibody responses were examined in rats with experimental ascending pyelonephritis caused by Escherichia coli O6K13H1. During 12-month follow-up of the infections, bacterial characteristics of the urinary and renal isolates were followed: O and K antigenicity, sensitivity to the bactericidal effect of normal human serum, capacity to attach to urinary tract epithelial cells, hemolytic activity, biochemical pattern, and virulence. During the long-term infection, the urinary and renal bacterial isolates changed in O and K antigenicity, serum sensitivity, and virulence. The adhesive capacity of the bacterial isolates did not change, possibly explaining the persistence of the bacteria in the urinary tract. The serum anti-O6 antibody levels remained high during the entire 1-year observation period, especially in the rats with renal involvement. Urinary anti-O6 antibodies were also found. The serum and urinary antibodies could have played a role in bringing about the observed changes in bacterial characteristics. Antibodies to lipid A were recorded in 9 of 16 rats with pyelonephritis and renal scarring and in 1 of 9 rats not having pyelonephritis or renal bacterial growth.     

5-Azacytidine produces differential undercondensation of alpha,beta and classical human satellite DNAs

Fluorescencein situ hybridization employing human alphoid, beta and classical satellite DNA probes was performed on 5-azacytidine treated and untreated chromosomes obtained from human lymphocytes. The individual used in this study presented a polymorphism of constitutive heterochromatin of chromosomes 1 and 9 as revealed byin situ digestion with the restriction endonucleaseAlul. Neither the alphoid nor the beta satellite DNA domains were susceptible to condensation-inhibition by 5-azacytidine. Only the classical satellite localized on chromosome 9 was affected. The constitutive heterochromatin size polymorphism was shown to depend mainly on variations of the classical satellite DNA domain. Therefore, condensation-inhibition, as a phenomenon which may modify the natural folding of the chromatin fibre, regionally affects human constitutive heterochromatin and seems to be dependent on the heterochromatic family.     

Localization of the chromosomal breakpoints of the t(12;16) in liposarcoma to subbands 12q13.3 and 16p11.2

Short-term cultures of two myxoid liposarcomas and two mixed-type (myxoid and round cell) liposarcomas were cytogenetically analyzed. A t(12;16)(q13;p11) was present in three tumors, whereas the fourth had an unbalanced 12;16-translocation with breaks in 12q13 and 12q22, with loss of the 12q13-q22 segment, and in 16p11. In the two mixed liposarcomas, the breakpoints could be determined at subband level to 12q13.3 and 16p11.2.     

The sympathetic innervation of the internal anal sphincter and rectum in the cat

The distribution of the sympathetic innervation to the internal anal sphincter (IAS) and rectum and the occurrence of different types of adrenergic receptors in the two organs were investigated in anaesthetized cats. Anal pressure and rectal motility were recorded by a manometric and a volumetric method respectively. Division of both the hypogastric nerves (HGN) and the lumbar colonic nerves (LCN) reduced the anal pressure by 46 +/- 6% of the resting pressure (40.9 +/- 6.4 mmHg) and consistently increased rectal motility. Efferent electrical stimulation of the HGN as well as the LCN elicited a contraction in the anus and the rectum, which, at maximal stimulation, caused the anal pressure to reach a similar level to that recorded before division of these nerves. After injection of phentolamine the anal contraction was abolished, whereas the rectal contraction was either abolished or converted to a beta-adrenergic relaxation. Propranolol caused increased rectal contraction in response to stimulation of the HGN and the LCN, whereas the anal contraction was unaffected. The results imply that the sympathetic nerves exert a tonic excitatory effect on the IAS and a dual effect on the rectum in the cat. The results also indicate that sympathetic fibres to the IAS are conveyed in both the HGN and the LCN. Inhibitory beta-adrenergic receptors seem to be of minor importance in regulating anal pressure.     

Acute myocarditis. Serologic diagnosis, clinical findings and follow-up

In a prospective study, 57 patients with a preliminary diagnosis of myocarditis were investigated. Twenty-four patients were considered to have an acute myocarditis, 14 had a suspected myocarditis, while in 19 patients myocarditis was excluded. Episodes of frequent supraventricular and/or ventricular extrasystoles during hospital stay were seen in 8/24 cases (33%) with myocarditis and in 1/19 cases (5%) without myocarditis. On follow-up 1 month later, no supraventricular extrasystoles were observed in either group. Echocardiographic signs consistent with left ventricular insufficiency were noted in 7/24 cases (29%) with myocarditis, in 1/14 cases (7%) with suspected myocarditis and in no case without myocarditis. With a "routine" serologic test battery covering influenza viruses A and B, adenovirus, Coxsackie virus group B, ECHO viruses, Chlamydia psittaci, Mycoplasma pneumoniae and hemolytic streptococci group A, a possible etiology could be documented in 9/24 cases (38%) with myocarditis and in 4/19 cases (21%) without myocarditis. Enterovirus-specific IgM was detected with solid-phase reverse immunosorbent test (SPRIST) in 12/23 (48%) cases with myocarditis and in 3/16 cases (19%) without myocarditis. In SPRIST-IgM-positive cases, IgM antibodies were detected in 15/20 (75%) of the sera taken on admission. The overall serological results indicated a recent infection in 16/24 cases (67%) with myocarditis and in 5/19 cases (26%) without myocarditis (p less than 0.05).     

The ionic mechanisms underlying N-methyl-D-aspartate receptor-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion

Activation of N-methyl-D-aspartate (NMDA) receptors can induce tetrodotoxin (TTX)-resistant membrane potential oscillations as well as fictive locomotion in the in vitro preparation of the lamprey spinal cord. The ionic basis of these oscillations were investigated in the presence of N-methyl-D,L-aspartate and TTX. Addition of blocking agents (2-amino-5-phosphonovalerate and tetraethylammonium (TEA)) and selective removal or substitution of certain ions (Mg2+, Ca2+, Na+, Ba2+) were used in the analysis of the oscillations. The depolarizing phase of the oscillation requires Na+ ions but not Ca2+ ions. The depolarization becomes larger if TEA is administered in the bath, which presumably is due to a blockade of potassium (K+) channels activated during the depolarizing phase. The repolarization appears to depend on a Ca2+ entry, which presumably acts indirectly by an activation of Ca2+-dependent K+ channels. Together with the NMDA-induced voltage dependence, this will bring the membrane potential back down to a hyperpolarized level.     

Capsaicin-sensitive non-cholinergic excitatory innervation of the guinea-pig tracheobronchial smooth muscle

Field stimulation of the isolated main bronchi of the guinea-pig results in a rapid contraction followed by a sustained contractile response. Tetrodotoxin abolished these effects. The first phase was strongly inhibited by hyoscine, indicating that it was mediated mainly by excitation of cholinergic nerves. The lasting contraction was abolished by capsaicin tachyphylaxis but it was resistant to the effects of hyoscine, hexamethonium or physostigmine. It is suggested that capsaicin-sensitive non-cholinergic nerves have major excitatory effect on the guinea-pig bronchial smooth muscle and there is also evidence for their influence on the trachea.     

Induction of tyrosine kinase receptor b by retinoic acid allows brain-derived neurotrophic factor-induced amyloid precursor protein gene expression in human SH-SY5Y neuroblastoma cells

Retinoic acid (RA) is a potent regulator of morphogenesis, growth and cell differentiation. Incubation with RA causes arrest of proliferation and neurite extension in SH-SY5Y cells, a neuroblastoma cell line of human origin. In these cells, RA regulates the expression of the β-amyloid precursor protein. The retinoid increases the levels of intracellular and secreted forms of APP (amyloid precursor protein), APP–mRNA levels and the activity of the APP promoter in transient transfection studies. These responses require long periods of exposition to the ligand, thus suggesting a nondirect effect of the RA receptors on the APP gene. Also in these cells, RA induces the expression of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), and 4 days of pretreatment with retinoic acid confers BDNF responsiveness to the APP promoter.