Chemotherapy in stage IV (metastatic) non-small-cell lung cancer. Provincial Lung Disease Site Group

After sciatic transection a strong decrease in immunoreactivity occurred, starting at 2 days. After 6, 10, 14, and 20 days survival only 5% of the sciatic motoneurons were strongly labeled for GluR2/3 against 80% in the control situation. From Day 20, GluR2/3 labeling started to increase again, reaching near normal levels at Day 80 after sciatic transection. In contrast, after sciatic crush, the decrease in GluR2/3 labeling in motoneurons was less pronounced and returned to normal in 30 days. In all animals, the GluR1 and GluR4 labeling of motoneurons remained unchanged after sciatic transection or crush. It is concluded that sciatic nerve injury leads to a strong, time-dependent decrease in the expression of GluR2 and 3 subunits in the corresponding motoneurons. As a consequence, AMPA receptors with a different subunit composition may be assembled, leading to a change in the functional properties of these receptors. Moreover, if they lack the GluR2 subunit, they may become calcium permeable.     

Recruitment of epidermal growth factor and transferrin receptors into coated pits in vitro: differing biochemical requirements

The biochemical requirements for epidermal growth factor (EGF) and transferrin receptor-mediated endocytosis were compared using perforated human A431 cells. Morphological studies showed that horseradish peroxidase (HRP)-conjugated EGF and gold-labeled antitransferrin (Tfn) receptor antibodies were colocalized during endocytosis in vitro. The sequestration of both ligands into deeply invaginated coated pits required ATP hydrolysis and cytosolic factors and was inhibited by GTP gamma S, indicating mechanistic similarities. Importantly, several differences in the biochemical requirements for sequestration of EGF and Tfn were also detected. These included differing requirements for soluble AP (clathrin assembly protein) complexes, differing cytosolic requirements, and differing sensitivities to the tyrosine kinase inhibitor, genistein. The biochemical differences detected between EGF and Tfn sequestration most likely reflect specific requirements for the recruitment of EGF-receptors (R) into coated pits. This assay provides a novel means to identify the molecular bases for these biochemical distinctions and to elucidate the mechanisms involved in ligand-induced recruitment of EGF-R into coated pits.     

Association of Sj?gren's syndrome with HLA-B8

HLA antigens were examined by microdroplet lymphocyte cytotoxicity in 31 patients with Sj?grens syndrome. Fifty percent of 22 Causcasian patients (7 of 17 females and 4 of 5 males) had HLA-B8, as compared to 21% of 1205 controls (P=0.002). The presence of HLA-B8 was not correlated with parotid salivary flow, keratoconjunctivitis sicca, or focus score. Because of its association with a number of autoimmune diseases, including Sj?gren's syndrome, it is suggested that HLA-B8 is genetically liked to an immune response gene(s) that predisposes the individual to autoimmune phenomena. The expression of autoimmunity may be determined by infectious or environmental factors.     

The effect of dopamine on neurohypophysial hormone release in vivo and from the rat neural lobe and hypothalamus in vitro

1. The rat hypothalamus (containing the supra-optic nuclei, paraventricular nuclei, median eminence and proximal pituitary stalk) has been incubated in vitro and shown to be capable of releasing the neurohypophysial hormones, oxytocin and arginine vasopressin, at a steady basal rate about one twentieth that of the rat neural lobe superfused in vitro. 2. The hypothalamus and neural lobe in vitro released both hormones in a similar arginine vasopressin/oxytocin ratio of about 1-2:1. However, when release was expressed relative to tissue hormone content, the hypothalamus was shown to release about three times as much arginine vasopressin and six times as much oxytocin as the neural lobe. 3. Dopamine in a concentration range of 10(-3)-10(-9)M caused graded increases in hormone release from the hypothalamus in vitro to a maximum fivefold increase over preceding basal levels. The demonstration that apomorphine also stimulated hormone release whereas noradrenaline was relatively ineffective suggested that a specific dopamine receptor was involved. A separate cholinergic component in the release process was indicated by the finding that acetylcholine stimulated release to a maximum fivefold increase in concentrations of 10(-3)-10(-9)M. 4. The fact that the isolated hypothalamus can be stimulated by dopamine and acetylcholine to release increased amount of oxytocin and arginine vasopressin raises the question of the origin and fate of the hormones released in this way. The possibility that they could be released into the hypophysial portal circulation from median eminence to affect the anterior lobe of the pituitary is discussed. 5. In similar doses, both dopamine and noradrenaline injected into the lateral cerebral ventricles of the brain of the anaesthetized, hydrated, lactating rat caused the release of arginine vasopressin and oxytocin. Apomorphine release both hormones but at a higher dose level and to less effect than the catecholamines. 6. The hormone release induced in vivo by dopamine could be prevented by the prior administration of haloperidol or phentolamine and these antagonists were equally effective in blocking the hormone release due to noradrenaline. The involvement of a specific dopamine receptor was more clearly implicated by the use of pimozide which completely inhibited the hormone release due to dopamine and apomorphine but not that due to noradrenaline. 7. It is suggested that the release of neurohypophysial hormones can be stimulated via a dopaminergic nervous pathway in addition to a cholinergic one. The possibility that the osmoreceptor mechanism for the release of antidiuretic hormone from the neural lobe of the pituitary may involve such a dopaminergic pathway is discussed.     

The effect of weather in modifying the pattern of pasture larval contamination with Ostertagia circumcincta

Serum complement activity, immunoglobulin levels and the circulating auto-antibodies were studied in the course of laser treatment of 20 cases of crural ulcer. After temporary changes a normalization of the humoral immune response was observed in the healing cases, while in the stagnating ones opposite trend was manifest. In none of the groups were detected circulating auto-antibodies against the investigated antigens.     

C1 inhibitor and diagnosis of hereditary angioedema in newborns

Symptoms of hereditary angioedema may present during the child's first years. Attacks may be a particular threat to the narrower airway of the child. An early diagnosis is most valuable because effective C1 inhibitor (C1 INH) concentrate is available. We present a reference area for the antigenic and functional determination of C1 INH by using uncontaminated umbilical cord blood from 80 normal newborns collected by puncturing vessels in the newly delivered placenta. We examined two full-term babies (1 and 2) from mothers with hereditary angioedema type I the same way. The concentration of C1 INH antigen was determined by radial immunodiffusion. The C1 INH functional assay was based on the addition of a known quantity of C1s, which enzymatically splits a chromogenic substrate. The test was performed in the presence of methylamine and heparin in a kinetic microtiter plate assay. Citrated plasma was used in both assays. The data obtained in the 80 cord blood samples (2.5-97.5 percentile) were 0.11-0.22 g/L for C1 INH antigen (adults, 0.15-0.33 g/L) and 47.2-85.9% for C1 INH function (percentage of adults). In cord blood, baby 1 had an antigenic value of 0.12 g/L (7.5 percentile) and C1 INH function of 61.8% (42 percentile). The corresponding values for baby 2 in cord blood were less than 0.05 g/L (0.106 g/L < 2.5 percentile) and 34.3% (12.9% < 2.5 percentile). Baby 2 had markedly lower C4 values yet much higher C4 activation products than baby 1. At 4 mo, baby 1 had an antigenic C1 INH value of 0.24 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional differences in the effects of amphetamine withdrawal on dopamine dynamics in the striatum. Analysis of circadian patterns using automated on-line microdialysis

The purpose of the study is to determine the relationship between behavioral symptoms of amphetamine withdrawal and the extracellular concentration of dopamine (DA) in the dorsolateral caudate nucleus and the nucleus accumbens across the entire light-dark cycle. This was accomplished using automated on-line microdialysis sampling in behaving rats. Animals were pretreated with escalating doses of d-amphetamine (or saline) over a 6-week period and then were withdrawn from amphetamine for 3, 7, or 28 days before testing. There were regional differences in the effects of amphetamine withdrawal on the concentrations of DA and DA metabolites in dialysate. Early during withdrawal (3 and 7 days), when animals showed postamphetamine withdrawal behavioral depression (nocturnal hypoactivity), there was a significant decrease in DA and DA metabolites in the dorsolateral caudate nucleus and a disruption in the normal circadian pattern of DA activity. In contrast, there was no effect of amphetamine withdrawal on DA dynamics in the nucleus accumbens. By 28 days after the discontinuation of amphetamine pretreatment, after basal DA in the caudate returned to normal, there was a significant increase in basal DA metabolism in both the caudate and the accumbens. This increase in DA metabolism may be related to the expression of sensitization, including a hypersensitivity to an amphetamine challenge. It is concluded that the role of the dorsal striatum in psychostimulant drug withdrawal syndromes deserves further consideration.