Distribution of galanin-binding sites in the monkey and human telencephalon: preliminary observations

Summary Using X-ray film autoradiography the distribution of ¹²⁵I-galanin binding sites was studied in the forebrain of monkey and man. In the monkey a high density was found in all areas of the neocortex, especially layer 4, and in certain subfields in the hippocampal region. Also in the human brain high activity was seen in neocortex, mainly layer 6 and in hippocampal areas, as well as in amygdala, piriform cortex and hypothalamus. These results suggest that the 29-amino acid peptide galanin may be involved in the regulation of higher cortical functions in primates.     

Functional relation between corticonuclear input and movements evoked on microstimulation in cerebellar nucleus interpositus anterior in the cat

The functional relation between receptive fields of climbing fibres projecting to the C1, C3 and Y zones and forelimb movements controlled by nucleus interpositus anterior via the rubrospinal tract were studied in cats decerebrated at the pre-collicular level. Microelectrode tracks were made through the caudal half of nucleus interpositus anterior. This part of the nucleus receives its cerebellar cortical projection from the forelimb areas of these three sagittal zones. The C3 zone has been demonstrated to consist of smaller functional units called microzones. Natural stimulation of the forelimb skin evoked positive field potentials in the nucleus. These potentials have previously been shown to be generated by climbing fibre-activated Purkinje cells and were mapped at each nuclear site, to establish the climbing fibre receptive fields of the afferent microzones. The forelimb movement evoked by microstimulation at the same site was then studied. The movements usually involved more than one limb segment. Shoulder retraction and elbow flexion were frequently evoked, whereas elbow extension was rare and shoulder protraction never observed. In total, movements at the shoulder and/or elbow occurred for 96% of the interpositus sites. At the wrist, flexion and extension movements caused by muscles with radial, central or ulnar insertions on the paw were all relatively common. Pure supination and pronation movements were also observed. Movements of the digits consisted mainly of dorsal flexion of central or ulnar digits. A comparison of climbing fibre receptive fields and associated movements for a total of 110 nuclear sites indicated a general specificity of the input-output relationship of this cerebellar control system. Several findings suggested that the movement evoked from a particular site would act to withdraw the area of the skin corresponding to the climbing fibre receptive field of the afferent microzones. For example, sites with receptive fields on the dorsum of the paw were frequently associated with palmar flexion at the wrist, whereas sites with receptive fields on the ventral side of the paw and forearm were associated with dorsiflexion at the wrist. Correspondingly, receptive fields on the lateral side of the forearm and paw were often associated with flexion at the elbow, whereas sites with receptive fields on the radial side of the forearm were associated with elbow extension. The proximal movements that were frequently observed also for distal receptive fields may serve to produce a general shortening of the limb to enhance efficiency of the withdrawal. It has previously been suggested that the cerebellar control of forelimb movements via the rubrospinal tract has a modular organisation. Each module would consist of a cell group in the nucleus interpositus anterior and its afferent microzones in the C1, C3 and Y zones, characterised by a homogenous set of climbing fibre receptive fields. The results of the present study support this organisational principle, and suggest that the efferent action of a module is to withdraw the receptive field from an external stimulus. Possible functional interpretations of the action of this system during explorative and reaching movements are discussed.     

On the relation among psychological distress,diabetes-related health behavior,and level of glycosylated hemoglobin in type I diabetes

This study aimed at investigating the relation between psychological diabetes-related health behavior, and metabolic aspects of diabetes. Fifty-one adult patients with type I diabetes mellitus took part in the study. Psychological status, health, and self-care behavior were assessed by means of questionnaires. Level of glycosylated hemoglobin (HbA(1c) served as the index of metabolic control. Depression was slightly elevated among women as was trait anxiety and blood-injury phobia or fear of medical interventions in all patients. Depression and anxiety were not related to duration of diabetes or presence of diabetes complications. As could be expected, patients who frequently checked their blood glucose level had a significantly lower level of HbA(1c) than those with infrequent checks. Patients with a marked blood-injury phobia carried out fewer daily checks of blood glucose level than those without, but blood-injury phobia was not directly related to HbA(tc) level. A higher level of HbA(tc) was, however, associated with mood deterioration. As depression was not related to health behavior, its effect on metabolic control is likely to be mediated via endocrine rather than behavioral variables.     

Thyrotropin-releasing hormone (TRH) counteracts neuronal damage induced by a substance P antagonist

Summary Intrathecal administration of the substance P antagonist Spantide caused marked necrotic changes of the gray matter of the spinal cord extending several segments from the injection site. Intravenous treatment with several doses of thyrotropin releasing hormone before and after Spantide injection completely prevented the necrotic lesion.     

Detecting Candida albicans in human milk

Procedures for diagnosis of mammary candidosis, including laboratory confirmation, are not well defined. Lactoferrin present in human milk can inhibit growth of Candida albicans, thereby limiting the ability to detect yeast infections. The inhibitory effect of various lactoferrin concentrations on the growth of C. albicans in whole human milk was studied. The addition of iron to the milk led to a two- to threefold increase in cell counts when milk contained 3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative culture results. This method may provide the necessary objective support needed for diagnosis of mammary candidosis.     

Molecular pathologic diagnosis in solid tumors. What is clinically relevant?

There are only a few clinically relevant applications of molecular pathology assays in solid tumors. Among the findings which may influence therapy decisions are the amplification of Her-2/new in breast cancer and specific translocations in sarcomas. Mutation analyses of p53 may be helpful for only a very few cases, e.g. for confirming high grade dysplasia in the upper gastrointestinal tract or for diagnosing malignant soft tissue tumors in isolated cases. Microsatellite analyses are important for HNPCC screening or distinguishing tissue specimens of questionable identity. Other applications of molecular pathology assays such as detection of minimal residual disease or tumor cell dissemination and FISH analysis of urine and effusion specimens, may be increasingly applied in the future.     

Perchlorate stimulates insulin secretion by shifting the gating of L-type Ca2+ currents in mouse pancreatic B-cells towards negative potentials

The effects of the chaotrophic anion perchlorate (ClO4-) on glucose-induced electrical activity, exocytosis and ion channel activity in mouse pancreatic B-cells were investigated by patch-clamp recordings and capacitance measurements. ClO4- stimulated glucose-induced electrical activity and increased the action potential frequency by 70% whilst not affecting the membrane potential when applied in the presence of a subthreshold concentration of the sugar. ClO4- did not influence ATP-dependent K (KATP) channel activity and voltage-gated delayed K+ current. Similarly, ClO4- had no effect on Ca2+-dependent exocytosis. The stimulation of electrical activity and insulin secretion was instead attributable to an enhancement of the whole-cell Ca2+ current. This effect was particularly pronounced at voltages around the threshold for action potential initiation and a doubling of the current amplitude was observed at -30 mV. This was due to a 7-mV shift in the gating of the Ca2+ current towards negative voltages. The action of ClO4- was more pronounced when added in the presence of 0.1 mM BAY K8644, whereas no stimulation was observed when applied at a maximal concentration of the agonist (1 mM). Single-channel recordings revealed that the effect of ClO4- on whole-cell currents was principally due to a 60% increase in the mean duration of the long openings and the number of active channels. We propose that ClO4- stimulates insulin secretion and electrical activity by exerting a BAY K8644-like action on Ca2+ channel gating.     

Evidence for striatal dopaminergic overactivity in paroxysmal dystonia indicated by microinjections in a genetic rodent model

Mutant dystonic hamsters (dt(sz)), a model of primary paroxysmal dystonia, display attacks of generalized dystonia in response to mild stress in an age-dependent manner. Recent studies in dystonic hamsters have revealed decreased densities of dopamine D(1) and D(2) in the dorsal striatum. This finding has been interpreted as a down-regulation in response to enhanced dopamine release because systemic treatments with neuroleptics reduced the severity of dystonia while levodopa exerted prodystonic effects. Therefore, in the present study we investigated the effects of amphetamine as well as of selective D(1) or D(2) receptor agonists and antagonists on the severity of dystonia after systemic administrations and after microinjections into the dorsal striatum. Amphetamine and the dopamine D(2) agonist quinpirole increased the severity of dystonia after systemic and striatal injections, while the dopamine D(1) agonist SKF 38393 exerted only moderate prodystonic effects after systemic administration of a high dose but not after striatal injections. These results suggest that a predominant overstimulation of D(2) receptors is pathogenetically involved in the dystonic syndrome. Combined systemic or striatal administrations of the D(1) and D(2) receptor agonists did not reveal synergistic prodystonic effects at the examined doses. The selective D(1) antagonist SCH 23390 as well as the D(2) antagonist raclopride tended to decrease the severity of dystonia after systemic administration but failed to exert significant effects after striatal injection. The coadministration of ineffective doses of the antagonists SCH 23390 and raclopride, however, exerted an enormous antidystonic efficacy after both systemic and striatal injections.Since striatal injections of compounds which enhance dopaminergic activity aggravated dystonia, while coinjections of dopamine D1 and D2 receptor antagonists reduced the severity of dystonia, the present findings clearly support the hypothesis that striatal dopaminergic overactivity plays a crucial role for the manifestation of dystonic attacks in the hamster model of paroxysmal dystonia.     

Detection of antibodies to HTLV-III in commercially available immunoglobulin preparations

Summary Samples of 96 polyvalent and virus-specific immunoglobulin batches commercially available in West-Germany were tested by enzyme-linked immunoassay and immunoblot for the presence of anti-HTLV-III antibodies. 37% of the polyvalent and 87% of the virus-specific batches were positive. It was concluded that these preparations are still safe and because of their reportedly low titer neutralizing antibodies possibly beneficial in certain cases, such as newborns of HTLV-III positive mothers or after accidental exposure to infectious material in clinics or laboratories.Abbreviations AIDS acquired immunodeficiency syndrome - ARC AIDS-related complex - CMV cytomegalovirus - ELISA enzyme-linked immuno adsorbent assay - HTLV-III human T-cell lymphotropic virus, type III