Arachidonic acid modulates [14C]stearic acid incorporation into phosphatidylinositol,in human neuroblastoma cells

In the human neuroblastoma cell line SK-N-BE(2), arachidonic acid (AA), supplied in the medium at micromolar concentrations, markedly ehnanced [¹⁴C]stearic acid (SA) (but not [¹⁴C]palmitic acid or [¹⁴C]oleic acid) incorporation into phosphatidylinositol (PtdIns). AA failed to stimulate [¹⁴C]SA incorporation into PtdIns precursors, namely phosphatidic acid and cytidinediphosphodiacylglycerol; furthermore, enhanced [¹⁴C]SA incorporation, brought about by exogenously administered AA, was not restricted to PtdIns tetraenoic species. When cells were pulsed for 1 h with [¹⁴C]SA (either in the presence or absence of AA) and then reincubated in AA- and [¹⁴C]SA-free medium, a marked loss of radioactivity from PtdIns was observed, that however was restricted to molecular species other than tetraenoic. These results are discussed in the light of possible mechanisms through which PtdIns achieves the 1-stearoyl-2-arachidonoyl configuration.     

Monoamines modulate the electrically-evoked efflux of 3H-choline from slices of guinea pig nucleus basalis magnocellularis

The influence exerted by monoamines on acetylcholine release was studied in electrically stimulated slices of guinea pig nucleus basalis magnocellularis (nbM) prelabelled with ³H-choline (3H-Ch).Noradrenaline, 30 M, and clonidine, 1 M, reduced the evoked ³H-Ch efflux by about 50%, but phenylephrine, 100 M. did not; idazoxan, 0.1 M. but not prazosin, 1 M, antagonized these effects. pointing to the involvement of alpha₂ receptors. Apomorphine, 1 or 30 M. reduced ³H-Ch efflux from nbM slices as well. The effect was shared by quinpirole, 1 or 10 M, but not by 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benz-azepine (SKF 38393). 10 M, and was antagonized by sulpiride, 1 M, but not by R-(+)-8-chloro-2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SCH 23390). 1 M, suggesting the involvement of the D₂ receptor subtype.5-hydroxytryptamine (5-HT) 0.3–30 M, and alphamethyl-5-HT, 10 M, significantly increased ³H-Ch efflux from nbM slices; the 5-HT₂ antagonist ritanserin, 1 M. prevented this response. 2-methyl-5-HT, 1–30 M, inhibited the evoked ³H-Ch efflux and its effect was prevented by the 5-HT₃ antagonist 1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222). 1 M.These findings indicate that i) catecholamines inhibit nbM neurons through alpha₂ and D₂ receptors and that ii) a complex serotonergic modulation of cholinergic function exists in the nbM, involving the activation of various receptor subtypes. which can mediate opposite responses. Correspondence to: A. Siniscalchi at the above address     

Glucocorticoids and androgens up-regulate the Zn-α2-glycoprotein messenger RNA in human breast cancer cells

Summary We have studied the hormonal regulation of the gene encoding Zn-₂-glycoprotein (Zn-₂-gp), a human protein with a high degree of amino acid sequence similarity to class I histocompatibility antigens that is produced by a specific subset of breast carcinomas. Northern blot analysis revealed that dexamethasone and 5-dihydrotestosterone strongly induced the accumulation of Zn-₂-gp mRNA in T-47D human breast cancer cells. Furthermore, the effect of these two hormones was shown to be additive, since the combination of both hormones produced a stimulation of Zn-₂-gp mRNA of at least 3-fold over that produced by either hormone alone. By contrast, the addition of 5-dihydrotestosterone, 17-estradiol, or progesterone failed to induce the expression of Zn-₂-gp. The stimulatory effect of glucocorticoids and androgens on Zn-₂-gp expression was produced in a time and dose dependent manner, without significantly affecting the cell proliferation rate. A time-course study demonstrated that the induction of Zn-₂-gp mRNA by androgens and glucocorticoids reached a level of 4 or 3.2-fold over the untreated control after seven days of incubation in the presence of a 10^–7 M concentration of 5-dihydrotestosterone or dexamethasone, respectively. A dose-response study showed that as little as 10^–11 M of 5-dihydrotestosterone or dexamethasone produced an accumulation of Zn-₂-gp mRNA of 2.4 or 2.1-fold over the control, respectively. On the basis of these results, we propose that Zn-₂-gp may be useful as a biochemical marker of breast carcinomas with a specific pattern of hormone responsiveness in whose development glucocorticoids and/or androgens may play a significant role.     

Renal tubular acidosis in the Silver-Russell syndrome

Several patients with the Silver-Russell syndrome (SRS) attending our Genetics Clinic were diagnosed as having persistent metabolic acidosis. Since this abnormality has not been reported previously in the SRS, we reexamined 33 SRS patients to evaluate the frequency and type of metabolic acidosis, the clinical and laboratory findings, and the growth pattern in SRS patients with and without metabolic acidosis. Among them, 14 had a consistent decrease in HCO levels. Renal studies in acidotic patients showed urine pH of 5.8 and 24 h urine calcium of <2.4 mg/kg/24 h; serum creatinine, excretion of glucose, and aminoacids were normal, as were renal ultrasound and excretory urography findings. These data supported the diagnosis of renal tubular acidosis, probably type II; the patients were treated with oral bicarbonate and acidosis was corrected successfully. Clinical manifestations were similar in acidotic and non-acidotic patients. The nutritional indices at diagnosis and at last evaluation (at least 8 months after diagnosis) were abnormally low in all patients; however, acidotic patients, treated with bicarbonate, showed an improvement of nutritional status particularly in the weight/height index, although the difference between groups after follow-up did not reach statistical significance. We suggest that metabolic acidosis due to renal tubular acidosis, probably type II, may occur in children with the SRS and should be looked for and treated in all patients. © 1995 Wiley-Liss, Inc.     

Pilot study of a visitor volunteer programme for community elderly people receiving home health care

There is a need to evaluate community support programmes for elderly people. In this randomized control trial (RCT), we determined the effectiveness of 'friendly visitors' in a volunteer programme of a visiting nurses organization in Southern Ontario, Canada. The Volunteer Friendly Visitor Programme was developed to support elderly people receiving homemaking and nursing care in the community. Volunteers are screened, trained, interviewed and matched to homebound elderly clients for general interest, visit expectations and personality. Volunteers spend three to four hours on average per week with clients socializing in mutually agreed-upon ways. The nursing staff identified clients who were lonely for this additional support. These newly-referred clients were randomly allocated to receive a friendly visitor or not for six weeks. Those receiving the volunteer visitor improved in life satisfaction and two social support measures: worth and social integration. Thus, the addition of volunteer visitors to planned homemaking and nursing care made a difference for elderly in the community.     

Kraepelin-oriented research-diagnosable schizophrenia,mania, and depression in schneider-negative schizophrenics

Summary The rigorous neo-Kraepelinean research criteria of the St. Louis/ Iowa and Taylor groups were applied to case record data of 116 first admissions of Schneider-negative schizophrenics—that is, those without first-rank symptoms (FRSs)—hospitalized in a strongly Schneider-oriented German University Psychiatric Clinic from 1962 to 1971. This sample had a total of 45.7% (53 cases) of psychiatric illness diagnosable by research methods. Indeed, only 31% (36 cases) of Schneider-negative schizophrenics turned out to have research-positive Kraepelin-oriented schizophrenia; and of these, 21 fulfilled both sets of research criteria for schizophrenia. It is important that 14.6% (17 cases) of Schneider-negative schizophrenia consisted of research-diagnosable affective disorder, with mania making up 5.2% and depression 9.4% of this figure. The findings suggest that a sample of Schneider-oriented schizophrenia without FRSs as routinely diagnosed in Germany does not seem to represent a clear-cut homogeneous and uncontaminated group of schizophrenics.     

The well-baby clinic

The termwell-baby clinic (literally, a clinic that concerns itself with healthy infants) is probably better known in the United States, where such clinics exist, than in central Europe, where, on the whole, they do not. For the convenience of readers accustomed to it a formal definition is proffered: A well-baby clinic is a service center, with emphasis on physical and mental hygiene and prophylaxis, where mothers are seen with their young, healthy infants and helped to understand and manage the infant's unfolding maturation [1: p. 5] and development [1: p. 5]. This may serve to differentiate well-baby clinics, on the one hand, from clinics for sick children and child guidance clinics (usually resorted to after disturbances have emerged) and, on the other hand, from maternity and child welfare clinics, whose primary object is to safeguard physical health. (Maternity and child welfare clinics are also known as family health clinics, child health clinics, and infant welfare clinics. The extent to which they can cater to the psychological needs of mother and infant depends on their staff's training.)This paper forms part of a research project entitled Childhood Pathology: Impact on Later Mental Health, which is being conducted at the Hampstead Child-Therapy Course and Clinic, London. The project is financed by National Institute of Mental Health Grant MH-05683-11. Appreciation is expressed to Anna Freud, Elizabeth Model, Professor A. J. Solnit, and Dr. Josefine Stross for their valuable suggestions. The authors acknowledge with gratitude the freedom to quote from the Well-Baby Clinic's annual reports, compiled by the clinic's pediatrician, Dr. Josefine Stross, with the active help of her past assistants, Annemarie Curson, Manna Friedmann, and Joyce Robertson, and her present assistants, Irene Freud and E. Model.This paper was originally published in German, in volume 2 of theJahrbuch der Psychohygiene, Ed. Gerd Biermann, Ernst Reinhardt Verlag, München/Basel, 1974.     

Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets.

Isolated rat hepatocyte couplets were used to perform the comparative study of two widely used immunosuppressors, cyclosporin A (CsA) and tacrolimus (FK506) on hepatocanalicular function. We assessed canalicular function by counting the percentage of couplets that were able to accumulate the fluorescent cholephile, cholyl-lysyl-fluorescein (CLF), into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA) of CLF. Compared to controls (DMSO-treated cells), CsA, in the approximate range of concentrations used therapeutically, caused inhibition of CVA of CLF, disorganization of the bile salt export pump (Bsep) localization at canalicular level resulting in its relocation into the cell, and disruption of the pericanalicular F-actin cytoskeleton. In contrast, FK506, at both approximately therapeutic and supratherapeutic concentrations, had no deleterious effect upon CVA of CLF, upon the localization of the bile salt transporter at the canalicular membrane, or on the organization of the pericanalicular F-actin cytoskeleton. These results point to transporter and cytoskeletal disorganization as contributors or determinants of CsA-induced cholestasis at canalicular level, whereas FK506 does not appear to produce these cholestasis-determining responses even at supratherapeutic concentrations.